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      Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort

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          Abstract

          Aim

          This study was conducted in order to evaluate the association between metformin use and clinical outcomes in type 2 diabetes mellitus (T2DM) patients hospitalized with coronavirus disease 2019 (COVID-19).

          Methods

          Patients with T2DM with confirmed diagnosis of COVID-19 and admitted between January 21, 2020, and January 31, 2021 in Hong Kong were identified in our cohort. Exposure was defined as metformin use within 90 days prior to admission until hospital discharge for COVID-19. Primary outcome was defined as clinical improvement of ≥1 point on the WHO Clinical Progression Scale (CPS). Other outcomes were hospital discharge, recovery, in-hospital death, acidosis, hyperinflammatory syndrome, length of hospitalization, and changes in WHO CPS score.

          Results

          Metformin use was associated with greater odds of clinical improvement (OR = 2.74, p = 0.009), hospital discharge (OR = 2.26, p = 0.009), and recovery (OR = 2.54, p = 0.005), in addition to lower odds of hyperinflammatory syndrome (OR = 0.71, p = 0.021) and death (OR = 0.41, p = 0.010) than control. Patients on metformin treatment had a shorter hospital stay (−2.76 days, p = 0.017) than their control counterparts. The average WHO CPS scores were significantly lower in metformin users than non-users since day 15 ( p < 0.001). However, metformin use was associated with higher odds of acidosis.

          Conclusions

          Metformin use was associated with lower mortality and lower odds for hyperinflammatory syndrome. This provides additional insights into the potential mechanisms of the benefits of metformin use in T2DM patients with COVID-19.

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          Most cited references38

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          A minimal common outcome measure set for COVID-19 clinical research

          Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.
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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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              The cytokine storm and COVID‐19

              Abstract Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of May 11, 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19. This article is protected by copyright. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                07 March 2022
                2022
                07 March 2022
                : 13
                : 810914
                Affiliations
                [1] 1 Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong , Hong Kong SAR, China
                [2] 2 Department of Family Medicine and Primary Care, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong , Hong Kong SAR, China
                [3] 3 Laboratory of Data Discovery for Health Limited , Hong Kong SAR, China
                [4] 4 Division of Endocrinology and Metabolism, Department of Medicine, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong , Hong Kong SAR, China
                [5] 5 World Health Organization (WHO) Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong , Hong Kong SAR, China
                Author notes

                Edited by: Susanna Hofmann, Helmholtz Association of German Research Centres (HZ), Germany

                Reviewed by: Jiandong Zhou, University of Oxford, United Kingdom; Theocharis Koufakis, University General Hospital of Thessaloniki AHEPA, Greece

                *Correspondence: Carlos K. H. Wong, carlosho@ 123456hku.hk

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.810914
                8935075
                35321338
                9132b497-6a5e-456a-a80f-a8a4c9bd94ab
                Copyright © 2022 Wong, Lui, Lui, Low, Kwok, Lau, Au, Xiong, Chung, Lau and Cowling

                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
                : 08 November 2021
                : 25 January 2022
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 39, Pages: 10, Words: 5827
                Funding
                Funded by: Food and Health Bureau , doi 10.13039/501100005407;
                Award ID: COVID190210
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                type 2 diabetes,metformin,covid-19,sars-cov-2,in-hospital mortality,hyperinflammatory syndrome

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