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Michaels TM, Essop MF, Joseph DE. Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells. Viruses 2024; 16:1243. [PMID: 39205219 PMCID: PMC11358987 DOI: 10.3390/v16081243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
The COVID-19 pandemic has revealed a bidirectional relationship between SARS-CoV-2 infection and diabetes mellitus. Existing evidence strongly suggests hyperglycemia as an independent risk factor for severe COVID-19, resulting in increased morbidity and mortality. Conversely, recent studies have reported new-onset diabetes following SARS-CoV-2 infection, hinting at a potential direct viral attack on pancreatic beta cells. In this review, we explore how hyperglycemia, a hallmark of diabetes, might influence SARS-CoV-2 entry and accessory proteins in pancreatic β-cells. We examine how the virus may enter and manipulate such cells, focusing on the role of the spike protein and its interaction with host receptors. Additionally, we analyze potential effects on endosomal processing and accessory proteins involved in viral infection. Our analysis suggests a complex interplay between hyperglycemia and SARS-CoV-2 in pancreatic β-cells. Understanding these mechanisms may help unlock urgent therapeutic strategies to mitigate the detrimental effects of COVID-19 in diabetic patients and unveil if the virus itself can trigger diabetes onset.
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Affiliation(s)
- Tara M. Michaels
- Centre for Cardio-Metabolic Research in Africa, Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7600, South Africa;
| | - M. Faadiel Essop
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa;
| | - Danzil E. Joseph
- Centre for Cardio-Metabolic Research in Africa, Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7600, South Africa;
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2
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Jayaraman AS, Darekar I, Dadhich NV, Tadepalli LSM, Gongwang Y, Singh S, Gavor E. Effect of the COVID-19 Pandemic on Respiratory Diseases and Their Economic Impacts. Pathogens 2024; 13:491. [PMID: 38921789 PMCID: PMC11206581 DOI: 10.3390/pathogens13060491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/23/2024] [Accepted: 05/29/2024] [Indexed: 06/27/2024] Open
Abstract
COVID-19 is an airborne respiratory disease that mainly affects the lungs. To date, COVID-19 has infected 580 million people with a mortality of approximately 7 million people worldwide. The emergence of COVID-19 has also affected the infectivity, diagnosis, and disease outcomes of existing diseases such as influenza, TB, and asthma in human populations. These are airborne respiratory diseases with symptoms and mode of transmission similar to those of COVID-19. It was speculated that the protracted nature of the COVID-19 pandemic coupled with vaccination could impact other respiratory diseases and mortality. In this study, we analyzed the impact of COVID-19 on flu, tuberculosis (TB), and asthma. Our analyses suggest that COVID-19 has a potential impact on the mortality of flu, TB, and asthma. These impacts vary across before the COVID-19 era, during the peak period of the pandemic, and after vaccinations/preventive measures were implemented, as well as across different regions of the world. Overall, the spread of flu generally reduced during the pandemic, resulting in a reduced expenditure on flu-related hospitalizations, although there were sporadic spikes at setting times. In contrast, TB deaths generally increased perhaps due to the disruption in access to TB services and reduction in resources. Asthma deaths, on the other hand, only marginally varied. Collectively, the emergence of COVID-19 added extra cost to the overall expenditure on some respiratory infectious diseases, while the cost for other infectious diseases was either reduced or somewhat unaffected.
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Affiliation(s)
- Ananya Sivaraman Jayaraman
- Global Indian International School, 27 Punggol Field Walk, Singapore 828649, Singapore; (A.S.J.); (I.D.); (N.V.D.); (L.S.M.T.)
| | - Ishita Darekar
- Global Indian International School, 27 Punggol Field Walk, Singapore 828649, Singapore; (A.S.J.); (I.D.); (N.V.D.); (L.S.M.T.)
| | - Nidhi Vijayprakash Dadhich
- Global Indian International School, 27 Punggol Field Walk, Singapore 828649, Singapore; (A.S.J.); (I.D.); (N.V.D.); (L.S.M.T.)
| | - Lakshmi Sai Manasvi Tadepalli
- Global Indian International School, 27 Punggol Field Walk, Singapore 828649, Singapore; (A.S.J.); (I.D.); (N.V.D.); (L.S.M.T.)
| | - Yao Gongwang
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (Y.G.); (S.S.)
| | - Sunil Singh
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (Y.G.); (S.S.)
| | - Edem Gavor
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (Y.G.); (S.S.)
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3
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Chume FC, Freitas PAC, Schiavenin LG, Sgarioni E, Leitao CB, Camargo JL. Glycated albumin in the detection of diabetes during COVID-19 hospitalization. PLoS One 2024; 19:e0297952. [PMID: 38498483 PMCID: PMC10947635 DOI: 10.1371/journal.pone.0297952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 01/14/2024] [Indexed: 03/20/2024] Open
Abstract
BACKGROUND Diabetes has emerged as an important risk factor for COVID-19 adverse outcomes during hospitalization. We investigated whether the measurement of glycated albumin (GA) may be useful in detecting newly diagnosed diabetes during COVID-19 hospitalization. METHODS In this cross-sectional test accuracy study we evaluated HCPA Biobank data and samples from consecutive in-patients, from 30 March 2020 to 20 December 2020. ROC curves were used to analyse the performance of GA to detect newly diagnosed diabetes (patients without a previous diagnosis of diabetes and admission HbA1c ≥6.5%). RESULTS A total of 184 adults (age 58.6 ± 16.6years) were enrolled, including 31 with newly diagnosed diabetes. GA presented AUCs of 0.739 (95% CI 0.642-0.948) to detect newly diagnosed diabetes. The GA cut-offs of 19.0% was adequate to identify newly diagnosed diabetes with high specificity (85.0%) but low sensitivity (48.4%). CONCLUSIONS GA showed good performance to identify newly diagnosed diabetes and may be useful for identifying adults with the condition in COVID-19-related hospitalization.
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Affiliation(s)
- Fernando Chimela Chume
- Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Faculty of Health Sciences, Universidade Zambeze, Beira, Mozambique
- Diabetes and Metabolism Group, Centro de Pesquisa Clínica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Priscila Aparecida Correa Freitas
- Diabetes and Metabolism Group, Centro de Pesquisa Clínica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Laboratory Diagnosis Division, Clinical Biochemistry Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Luisa Gazzi Schiavenin
- Diabetes and Metabolism Group, Centro de Pesquisa Clínica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Eduarda Sgarioni
- Experimental Research Centre, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Cristiane Bauermann Leitao
- Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Diabetes and Metabolism Group, Centro de Pesquisa Clínica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Joíza Lins Camargo
- Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Diabetes and Metabolism Group, Centro de Pesquisa Clínica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Experimental Research Centre, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
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Tsikala Vafea M, Traboulsi C, Stefanovic-Racic M. Lower Glycosylated Hemoglobin Is Associated With Lower In-Hospital Mortality in Patients With COVID-19: A Systematic Review of the Literature and Meta-Analysis. Endocr Pract 2024; 30:70-77. [PMID: 37769967 DOI: 10.1016/j.eprac.2023.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/02/2023] [Accepted: 09/18/2023] [Indexed: 10/03/2023]
Abstract
OBJECTIVE Poor glycemic control during COVID-19 hospitalization is associated with higher mortality. However, the association between long-term glycemic control, as reflected by the glycosylated hemoglobin (HbA1c) and outcomes has yet to be clarified, with some studies reporting no association. The aim of this study is to determine the association between HbA1c and in-hospital mortality in patients with COVID-19. METHODS Pubmed, Embase, and Web of Science databases were searched for studies examining the association between HbA1c level and in-hospital COVID-19 mortality. Random-effects meta-analysis was performed. Heterogeneity was assessed using the I2 statistic. Publication bias was assessed using funnel plots. RESULTS Among 4142 results, 22 studies were included in the final analysis with a total of 11 220 patients. Lower Hba1c was associated with lower in-hospital mortality [odds ratio (OR), 0.53; 95% CI, 0.37-0.76; I2 81%], in using HbA1c as a dichotomous variable. When only patients with diabetes were included in the analysis, the association remained statistically significant (OR, 0.67; 95% CI, 0.47-0.96). In the subgroup analysis, the association remained statistically significant in studies using as cutoff the HbA1c value of 6.5% (OR, 0.34; 95% CI, 0.15-0.77) and 7% (OR, 0.54; 95% CI 0.32-0.90), but not with greater HbA1c cutoff values; 7.5% and ≥8%. In studies using HbA1C as a continuous variable, HbA1c level did not have a statistically significant association with in-hospital mortality, either in univariate or multivariate analyses. CONCLUSION A better glycemic control prior to hospitalization, as reflected by lower HbA1c, is associated with lower in-hospital mortality in patients with COVID-19.
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Affiliation(s)
- Maria Tsikala Vafea
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
| | - Cindy Traboulsi
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Maja Stefanovic-Racic
- Department of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Balintescu A, Rysz S, Hertz C, Grip J, Cronhjort M, Oldner A, Svensen C, Mårtensson J. Prevalence and impact of chronic dysglycaemia among patients with COVID-19 in Swedish intensive care units: a multicentre, retrospective cohort study. BMJ Open 2023; 13:e071330. [PMID: 37730398 PMCID: PMC10510869 DOI: 10.1136/bmjopen-2022-071330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 08/29/2023] [Indexed: 09/22/2023] Open
Abstract
OBJECTIVE Using glycated haemoglobin A1c (HbA1c) screening, we aimed to determine the prevalence of chronic dysglycaemia among patients with COVID-19 admitted to the intensive care unit (ICU). Additionally, we aimed to explore the association between chronic dysglycaemia and clinical outcomes related to ICU stay. DESIGN Multicentre retrospective observational study. SETTING ICUs in three hospitals in Stockholm, Sweden. PARTICIPANTS COVID-19 patients admitted to the ICU between 5 March 2020 and 13 August 2020 with available HbA1c at admission. Chronic dysglycaemia was determined based on previous diabetes history and HbA1c. PRIMARY AND SECONDARY OUTCOMES Primary outcome was the actual prevalence of chronic dysglycaemia (pre-diabetes, unknown diabetes or known diabetes) among COVID-19 patients. Secondary outcome was the association of chronic dysglycaemia with 90-day mortality, ICU length of stay, duration of invasive mechanical ventilation (IMV) and renal replacement therapy (RRT), accounting for treatment selection bias. RESULTS A total of 308 patients with available admission HbA1c were included. Chronic dysglycaemia prevalence assessment was restricted to 206 patients admitted ICUs in which HbA1c was measured on all admitted patients. Chronic dysglycaemia was present in 82.0% (95% CI 76.1% to 87.0%) of patients, with pre-diabetes present in 40.2% (95% CI 33.5% to 47.3%), unknown diabetes in 20.9% (95% CI 15.5% to 27.1%), well-controlled diabetes in 7.8% (95% CI 4.5% to 12.3%) and uncontrolled diabetes in 13.1% (95% CI 8.8% to 18.5%). All patients with available HbA1c were included for the analysis of the relationship between chronic dysglycaemia and secondary outcomes. We found no independent association between chronic dysglycaemia and 90-day mortality, ICU length of stay or duration of IMV. After excluding patients with specific treatment limitations, no association between chronic dysglycaemia and RRT use was observed. CONCLUSIONS In our cohort of critically ill COVID-19 patients, the prevalence of chronic dysglycaemia was 82%. We found no robust associations between chronic dysglycaemia and clinical outcomes when accounting for treatment limitations.
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Affiliation(s)
- Anca Balintescu
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden
| | - Susanne Rysz
- Department of Perioperative Medicine and Intensive Care, Karolinska Institute, Stockholm, Sweden
| | - Carl Hertz
- Department of Anesthesia and Intensive Care, Stockholm South General Hospital Anaesthesia, Stockholm, Sweden
| | - Jonathan Grip
- Department of Perioperative Medicine and Intensive Care, Karolinska Institute, Stockholm, Sweden
| | - Maria Cronhjort
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden
| | - Anders Oldner
- Department of Perioperative Medicine and Intensive Care, Karolinska Institute, Stockholm, Sweden
| | - Christer Svensen
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden
| | - Johan Mårtensson
- Department of Perioperative Medicine and Intensive Care, Karolinska Institute, Stockholm, Sweden
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Gojda J, Koudelková K, Ouřadová A, Lang A, Krbcová M, Gvozdeva A, Šebo V, Slagmolen L, Potočková J, Tůma P, Rossmeislová L, Anděl M, Karpe F, Schlesinger S. Severe COVID-19 associated hyperglycemia is caused by beta cell dysfunction: a prospective cohort study. Nutr Diabetes 2023; 13:11. [PMID: 37460458 DOI: 10.1038/s41387-023-00241-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 05/11/2023] [Accepted: 06/29/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND COVID-19, an infectious disease caused by SARS-CoV-2, was shown to be associated with an increased risk of new-onset diabetes. Mechanisms contributing to the development of hyperglycemia are still unclear. We aimed to study whether hyperglycemia is related to insulin resistance and/or beta cell dysfunction. MATERIALS AND METHODS Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: corticosteroids use, indirect calorimetry, and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI). Resting energy expenditure (REE) and respiratory quotient (RQ) was calculated from the gas exchange and nitrogen losses. RESULTS 26 patients (out of 37) with complete outcome data were included in the analysis (age ~59.0 years; BMI ~ 30.4, 35% women). Patients were hypermetabolic at T0 (30.3 ± 4.0 kcal/kg lean mass/day, ~120% predicted) but REE declined over 6 months (ΔT6-T0 mean dif. T6-T0 (95% CI): -5.4 (-6.8, -4.1) kcal/kg FFM/day, p < 0.0001). 17 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity in T0 was similarly low in hyperglycemic (H) and normoglycemic patients (N) (T0 ISIH = 3.12 ± 1.23, ISIN = 3.47 ± 1.78, p = 0.44), whereas insulin response was lower in the H group (DIH = 3.05 ± 1.79 vs DIN = 8.40 ± 5.42, p = 0.003). Over 6 months ISI (ΔT6-T0 mean dif. T6-T0 for ISI (95% CI): 1.84 (0.45, 3.24), p = 0.01)) increased in the H group only. CONCLUSIONS Patients with severe COVID-19 had increased REE and insulin resistance during the acute phase due to the infection and corticosteroid use, but these effects do not persist during the follow-up period. Only patients with insufficient insulin response developed hyperglycemia, indicating that beta cell dysfunction, rather than insulin resistance, was responsible for its occurrence.
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Affiliation(s)
- Jan Gojda
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic.
| | - Kateřina Koudelková
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Anna Ouřadová
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Alexander Lang
- Institute for Biometrics and Epidemiology, German Diabetes Center (Deutsches Diabetes-Zentrum/DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
| | - Magdaléna Krbcová
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Alexandra Gvozdeva
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Viktor Šebo
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Lotte Slagmolen
- Faculty of Movement and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Jana Potočková
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Petr Tůma
- Department of Hygiene, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Lenka Rossmeislová
- Institute for Biometrics and Epidemiology, German Diabetes Center (Deutsches Diabetes-Zentrum/DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michal Anděl
- Department of Internal Medicine, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Fredrik Karpe
- Oxford Center for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, UK
| | - Sabrina Schlesinger
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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Kandinata SG, Soelistijo SA, Pranoto A, Triyono EA. Random Blood Glucose, but Not HbA1c, Was Associated with Mortality in COVID-19 Patients with Type 2 Diabetes Mellitus-A Retrospective Study. PATHOPHYSIOLOGY 2023; 30:136-143. [PMID: 37092526 PMCID: PMC10123645 DOI: 10.3390/pathophysiology30020012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 03/05/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023] Open
Abstract
Previous studies have yielded inconsistent results on whether glycated hemoglobin (HbA1c) and random blood glucose (RBG) are associated with mortality of coronavirus disease 2019 (COVID-19) patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the association of HbA1c and RBG with mortality among COVID-19 patients with T2DM. A retrospective study was conducted on 237 patients with COVID-19 and T2DM (survival (n = 169) and non-survival groups (n = 68)). Data on socio-demography, comorbidities, clinical symptoms, laboratory examination, and mortality were collected. Patients in the non-survival group had an older age range as compared with those in the survival group (60 (52.3-65.0) vs. 56.0 (48.5-61.5) years, p = 0.009). There was no statistical gender difference between the two groups. After matching was done, chronic kidney disease, NLR, d-dimer, procalcitonin, and random blood glucose were higher in the non-survival group compared to the survival group (p < 0.05). HbA1c levels were similar in survivors and non-survivors (8.7% vs. 8.9%, p=0.549). The level of RBG was independently associated with mortality of COVID-19 patients with T2DM (p = 0.003, adjusted OR per 1-SD increment 2.55, 95% CI: 1.36-4.76). In conclusion, RBG was associated with the mortality of COVID-19 patients with T2DM, but HbA1c was not.
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Affiliation(s)
- Stefanus Gunawan Kandinata
- Department of Internal Medicine, Dr. Soetomo General Academic Hospital—Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Soebagijo Adi Soelistijo
- Endocrinology, Metabolism and Diabetes Unit, Department of Internal Medicine, Dr. Soetomo General Academic Hospital—Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Agung Pranoto
- Endocrinology, Metabolism and Diabetes Unit, Department of Internal Medicine, Dr. Soetomo General Academic Hospital—Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
| | - Erwin Astha Triyono
- Tropical and Infectious Disease Unit, Department of Internal Medicine, Dr. Soetomo General Academic Hospital—Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
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Chourasia P, Goyal L, Kansal D, Roy S, Singh R, Mahata I, Sheikh AB, Shekhar R. Risk of New-Onset Diabetes Mellitus as a Post-COVID-19 Condition and Possible Mechanisms: A Scoping Review. J Clin Med 2023; 12:1159. [PMID: 36769807 PMCID: PMC9917823 DOI: 10.3390/jcm12031159] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/11/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Long-term effects of COVID-19 are becoming more apparent even as the severity of acute infection is decreasing due to vaccinations and treatment. In this scoping review, we explored the current literature for the relationship between COVID-19 infection and new-onset diabetes mellitus four weeks after acute infection. We systematically searched the peer-reviewed literature published in English between 1 January 2020 and 31 August 2022 to study the risk of new-onset diabetes mellitus post-COVID-19 infection. This scoping review yielded 11 articles based on our inclusion and exclusion criteria. Except for one, all studies suggested an increased risk of new-onset diabetes mellitus 4 weeks after acute infection. This risk appears most in the first six months after the acute COVID-19 infection and seems to increase in a graded fashion based on the severity of the initial COVID-19 infection. Our review suggests a possible association of new-onset diabetes mellitus 4 weeks after acute COVID-19 infection. Since the severity of COVID-19 infection is associated with the development of post-infectious diabetes, vaccination that reduces the severity of acute COVID-19 infection might help to reduce the risk of post-COVID-19 diabetes mellitus. More studies are needed to better understand and quantify the association of post-COVID-19 conditions with diabetes and the role of vaccination in influencing it.
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Affiliation(s)
- Prabal Chourasia
- Department of Hospital Medicine, Mary Washington Hospital, Fredericksburg, VA 22401, USA
| | - Lokesh Goyal
- Department of Hospital Medicine, Christus Spohn Hospital Corpus Christ, Shoreline, TX 78404, USA
| | - Dhruv Kansal
- Yale Waterbury Internal Medicine Program, Waterbury Hospital, Waterbury, CT 06708, USA
| | - Sasmit Roy
- Department of Nephrology, Centra Lynchburg General Hospital, Lynchburg, VA 24501, USA
| | - Rohit Singh
- Department of Hemato-Oncology, University of Vermont Medical Center, Burlington, VT 05401, USA
| | - Indrajeet Mahata
- Department of Cardiology, University of Missouri, Springfield, MO 65804, USA
| | - Abu Baker Sheikh
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87106, USA
| | - Rahul Shekhar
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87106, USA
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9
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Al-Jubury KS, K OA, Alshareef DKJ, Al-Jubury M, Jameel MI. D-dimer and HbA1c levels findings in COVID-19 Iraqi patients. BRAZ J BIOL 2023; 84:e266823. [PMID: 36629638 DOI: 10.1590/1519-6984.266823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 11/18/2022] [Indexed: 01/11/2023] Open
Abstract
On March 11, 2020, the World Health Organization (WHO) declared a new coronavirus infection caused by the SARS-CoV-2 virus as a pandemic, making it the 11th pandemic of the 20th and 21st centuries. This study investigated the clinical and laboratory results (D-dimer, conventional coagulation, and HbA1c biomarker concentrations) of 150 patients (75 male and 75 female) with confirmed COVID-19 pneumonia and 50 controls (25 male and 25 female). For disease diagnosis, all COVID-19 patients were given a Real-Time Reverse Transcription Polymerase Chain Reaction Assay (RT-PCR). The findings revealed that D-dimer and HbA1c levels in COVID-19 patients were significantly higher (P 0.001) at the time of admission; In COVID-19 patients, there was also a strong correlation between D-dimer levels and HbA1c levels (P 0.001). In conclusion, COVID-19 patients are more likely to have a poor prognosis if their D-dimer and HbA1c levels remain uncontrolled over a lengthy period. To lower the likelihood of a bad prognosis in COVID-19, patients with higher levels of D-dimer and HbA1c should be continuously monitored.
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Affiliation(s)
- K S Al-Jubury
- Iraqi Ministry of Health, Baghdad Medical City, Training and Human Development Center, Baghdad, Iraq
| | - O Abdulmunem K
- Iraqi Ministry of Health, Baghdad Medical City, Training and Human Development Center, Baghdad, Iraq
| | - D K J Alshareef
- Iraqi Ministry of Health, Baghdad Medical City, Training and Human Development Center, Baghdad, Iraq
| | - M Al-Jubury
- University College Dublin, College of Science, Dublin, Ireland
| | - M I Jameel
- Koya University, Faculty of Science and Health, Department of Medical Microbiology, Koya, Kurdistan Region, Iraq
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10
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Rhou YJJ, Hor A, Wang M, Wu YF, Jose S, Chipps DR, Cheung NW. Dexamethasone-induced hyperglycaemia in COVID-19: Glycaemic profile in patients without diabetes and factors associated with hyperglycaemia. Diabetes Res Clin Pract 2022; 194:110151. [PMID: 36375566 PMCID: PMC9651935 DOI: 10.1016/j.diabres.2022.110151] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 10/05/2022] [Accepted: 11/06/2022] [Indexed: 11/13/2022]
Abstract
AIMS To evaluate glycaemic profiles of COVID-19 patients without diabetes receiving dexamethasone and determine factors associated with hyperglycaemia. METHODS All subjects without pre-existing diabetes receiving dexamethasone 6 mg for COVID-19 in a non-critical care setting were identified. Glucose profiles were obtained from capillary blood glucose (BG). Univariate and multivariate analyses were performed to identify factors associated with dexamethasone-induced hyperglycaemia (BG ≥ 10 mmol/L). RESULTS Of 254 subjects, 129 (50.8%) were male with age 51.1 ± 18.2 years and weight 89.7 ± 26.3 kg. Hyperglycaemia post-dexamethasone occurred in 121 (47.6%). Glucose excursions began within three hours (6.8 ± 1.4 mmol/L pre-dexamethasone vs 8.7 ± 2.4 mmol/L at ≤ 3 h, p < 0.001) and peaked at 7-9 h (10.5 ± 2.3 mmol/L, p < 0.001 vs pre-dexamethasone). BGs post-intravenous were higher than post-oral administration for the initial six hours. Hyperglycaemic subjects were older (57.8 ± 17.5 years vs 45.0 ± 16.6 years, p < 0.001), had higher initial glucose (6.3 ± 1.0 vs 5.9 ± 0.9 mmol/L, p = 0.004), higher HbA1c (5.8 ± 0.3% [40 ± 3.5 mmol/mol] vs 5.5 ± 0.4% [37 ± 4.1 mmol/mol], p < 0.001) higher C-reactive protein (CRP) (100 ± 68 vs 83 ± 58 mg/L, p = 0.026), and lower eGFR (79 ± 17 vs 84 ± 16 mL/min/1.73 m2, p = 0.045). Mortality was greater in the hyperglycaemia group (9/121 [7.4%] vs 2/133 [1.5%], p = 0.02). Age, HbA1c and CRP were independently associated with hyperglycaemia. CONCLUSIONS Half of subjects without diabetes experienced hyperglycaemia post-dexamethasone for COVID-19, peak occurring after 7-9 h. Age, HbA1c and CRP were associated with hyperglycaemia.
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Affiliation(s)
- Yoon Ji J Rhou
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
| | - Amanda Hor
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia
| | - Mawson Wang
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
| | - Yu-Fang Wu
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
| | - Suja Jose
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
| | - David R Chipps
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
| | - N Wah Cheung
- Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
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11
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Kodali R, Umesh S, Selvam S, Kamath D, Shobha V. Timing of tofacitinib therapy is critical to improving outcomes in severe-critical COVID-19 infection: A retrospective study from a tertiary care hospital. Medicine (Baltimore) 2022; 101:e30975. [PMID: 36316872 PMCID: PMC9622334 DOI: 10.1097/md.0000000000030975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 09/06/2022] [Indexed: 11/07/2022] Open
Abstract
Describe the use of tofacitinib in severe and critical coronavirus disease-2019 (COVID-19), and explore the association of drug initiation time with survival. A retrospective study of inpatients with severe or critical COVID-19 at a tertiary care hospital, who were prescribed generic tofacitinib for at least 48 hours, was conducted. Baseline demographics, comorbidities, illness severity, treatment, adverse effects and outcomes were analyzed. Patients were grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Forty-one patients ([85.4% males], mean age 52.9 ± 12.5 years), were studied. 65.9% (n = 27) had severe COVID-19, while 34.1% (n = 14) were critically ill. Death occurred in 36.6% patients (n = 15). The median time to prescription of tofacitinib was 13 (9.50, 16.0) days of symptom onset. Tofacitinib was initiated early (8-13 days) in 56.1% of patients (n = 23), while the remaining received it beyond day 14 of symptom onset (late initiation group). Multivariate logistic regression adjusted for age, presence of diabetes mellitus and illness duration prior to hospitalization demonstrated higher odds of survival (adjusted odds ratio 19.3, 95% confidence interval 2.57, 145.2) in the early initiation group, compared to the late initiation group. Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds.
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Affiliation(s)
- Ramya Kodali
- Department of Clinical Immunology and Rheumatology, St. John’s Medical College Hospital, Bengaluru, Karnataka, India
| | - Soumya Umesh
- Department of Internal Medicine, St. John’s Medical College Hospital, Bengaluru, Karnataka, India
| | - Sumithra Selvam
- Division of Epidemiology and Biostatistics, St. John’s Research Institute, St. John’s Medical College Hospital, Bengaluru, Karnataka, India
| | - Deepak Kamath
- Department of Pharmacology, St. John’s Medical College Hospital, Bengaluru, Karnataka, India
| | - Vineeta Shobha
- Department of Clinical Immunology and Rheumatology, St. John’s Medical College Hospital, Bengaluru, Karnataka, India
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12
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Gavkare AM, Nanaware N, Rayate AS, Mumbre S, Nagoba BS. COVID-19 associated diabetes mellitus: A review. World J Diabetes 2022; 13:729-737. [PMID: 36188145 PMCID: PMC9521440 DOI: 10.4239/wjd.v13.i9.729] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/20/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
A significantly higher rate of new-onset diabetes in many coronavirus disease 2019 (COVID-19) patients is a frequently observed phenomenon. The resultant hyperglycemia is known to influence the clinical outcome, thereby increasing the cost of treatment and stay in hospital. This will also affect the post-hospitalization recuperation. It has been observed that new-onset diabetes in COVID-19 patients is associated with considerable increase in morbidity and may be associated with increased mortality in some cases. This mini-review focuses on the possible causes to understand how COVID-19-related diabetes develops, various associated risk factors, and possible mechanism to understand the natural history of the disease process, clinical outcome, associated morbidities and various treatment options in the mana-gement of post COVID-19 diabetes. A literature search was performed in PubMed and other online database using appropriate keywords. A total of 80 articles were found, among which, 53 of the most relevant were evaluated/ analyzed and relevant data were included. The studies show that patients who have had severe acute respiratory syndrome coronavirus 2 infection leading to development of COVID-19 may manifest not only with new-onset diabetes but also worsening of pre-existing diabetes. Cytopathic effect and autoimmune destruction of insulin-secreting pancreatic beta cells, cytokine storm during the active phase of infection causing impaired insulin secretion and resistance, drug-induced hyperglycemia, undetected pre-existing hyperglycemia/diabetic condition, and stress-induced impairment of glucose metabolism are some of the possible potential mechanisms of COVID-19-associated new-onset diabetes mellitus. Many studies published in recent times have found a significantly higher rate of new-onset diabetes mellitus in many COVID-19 patients. Whether it is an inflammatory or immune-mediated response, direct effect of virus or combination of these is unclear. The resultant hyperglycemia is known to influence the clinical outcome and has been associated with considerable increase in morbidity and increased mortality in some cases.
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Affiliation(s)
- Ajay M Gavkare
- Physiology, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, Maharashtra, India
| | - Neeta Nanaware
- Physiology, Vilasrao Deshmukh Government Medical College, Latur 413512, Maharashtra, India
| | - Abhijit S Rayate
- Surgery, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, Maharashtra, India
| | - Sachin Mumbre
- Community Medicine, Ashwini Rural Medical College, Solapur 413006, Maharashtra, India
| | - Basavraj S Nagoba
- Microbiology, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, Maharashtra, India
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13
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Numaguchi R, Kurajoh M, Hiura Y, Imai T, Morioka T, Saito M, Shiraishi S, Emoto M, Nishiguchi Y. Glycated hemoglobin level on admission associated with progression to severe disease in hospitalized patients with non-severe coronavirus disease 2019. J Diabetes Investig 2022; 13:1779-1787. [PMID: 35616179 PMCID: PMC9348501 DOI: 10.1111/jdi.13845] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 05/06/2022] [Accepted: 05/24/2022] [Indexed: 12/15/2022] Open
Abstract
Aims/Introduction Poor glycemic control is known to be associated with severe infection development. This retrospective observational study examined whether glycemic control before coronavirus disease 2019 (COVID‐19) onset contributes to progression from non‐severe to severe COVID‐19. Materials and Methods Glycated hemoglobin (HbA1c) was measured on hospital admission in 415 patients with non‐severe COVID‐19. The outcome was determined from time of hospital admission to severe progression, based on clinical practice guidelines for COVID‐19 in Japan. Results The median value for HbA1c on admission was 6.1%, with diabetes present in 138 patients (33.3%). Among the total cohort, 93 (22.4%) progressed to severe COVID‐19 with a median (interquartile range) time of 4 days (3–7 days), whereas 322 (77.6%) were discharged after 13 days (10–17 days). A multivariable Cox proportional hazards regression model showed that HbA1c level on admission was independently associated with progression to severe COVID‐19 (hazard ratio for 1% increase 1.237, 95% confidence interval 1.037–1.475; P = 0.018), with findings consistent among several sensitivity analyses. In subgroup analyses, such an association was significant in patients with diabetes, as well as older age, current smoking habit, lower estimated glomerular filtration rate, higher C‐reactive protein level, moderate II COVID‐19, dyslipidemia and chronic respiratory disease, with no remarkable inconsistency among the subgroups. Finally, higher HbA1c level (≥7%) was more strongly associated with severe COVID‐19 progression than diabetes. Conclusions The results suggest that poor glycemic control before COVID‐19 onset contributes to progression from non‐severe to severe COVID‐19, even in patients with severe COVID‐19 risk factors regardless of the presence of diabetes.
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Affiliation(s)
- Ryutaro Numaguchi
- Department of Diabetes and Endocrinology, Osaka City Juso Hospital, Osaka, Japan
| | - Masafumi Kurajoh
- Department of Metabolism, Endocrinology, and Molecular Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yoshikazu Hiura
- Department of Diabetes and Endocrinology, Osaka City Juso Hospital, Osaka, Japan
| | - Takumi Imai
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Tomoaki Morioka
- Department of Metabolism, Endocrinology, and Molecular Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Mika Saito
- Department of Pediatrics, Osaka City Juso Hospital, Osaka, Japan
| | - Satoshi Shiraishi
- Department of Respiratory Medicine, Osaka City Juso Hospital, Osaka, Japan
| | - Masanori Emoto
- Department of Metabolism, Endocrinology, and Molecular Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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14
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Glycated Albumin and Glycated Albumin/HbA1c Predict the Progression of Coronavirus Disease 2019 from Mild to Severe Disease in Korean Patients with Type 2 Diabetes. J Clin Med 2022; 11:jcm11092327. [PMID: 35566453 PMCID: PMC9105907 DOI: 10.3390/jcm11092327] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/16/2022] [Accepted: 04/19/2022] [Indexed: 12/15/2022] Open
Abstract
Hyperglycemia is among the main risk factors for severe COVID-19. We evaluated the association of glycated albumin (GA) and GA/HbA1c ratio with progression of COVID-19 from mild to severe disease in patients with type 2 diabetes mellitus (T2DM). Our retrospective study included 129 patients aged over 18 years with COVID-19 and T2DM who did not have any need of oxygen supplement. Of these, 59 patients whose COVID-19 was aggravated and required oxygen supplementation eventually were classified as having severe disease. Clinical and laboratory data were compared between mild and severe cases. The median of GA (18.4% vs. 20.95%, p = 0.0013) and GA/HbA1c (2.55 vs. 2.68, p = 0.0145) were higher in severe disease than in mild disease and positively correlated with C-reactive protein (Kendal Tau coefficient 0.200 and 0.126, respectively; all p < 0.05). Multiple logistic regression analysis showed that GA (odds ratio (OR), 1.151; 95% confidence interval (CI), 1.024−1.294) and GA/HbA1c (OR, 8.330; 95% CI, 1.786−38.842) increased the risk of severe disease. Patients with GA 20% or higher were 4.03 times more likely to progress from mild to severe disease. GA and GA/HbA1c ratio predicted progression of COVID-19 from mild to severe disease in patients with T2DM.
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15
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Tzeravini E, Stratigakos E, Siafarikas C, Tentolouris A, Tentolouris N. The Role of Diabetes and Hyperglycemia on COVID-19 Infection Course-A Narrative Review. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2022; 3:812134. [PMID: 36992740 PMCID: PMC10012165 DOI: 10.3389/fcdhc.2022.812134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/31/2022] [Indexed: 01/08/2023]
Abstract
It was previously reported that subjects with diabetes mellitus (DM) are more vulnerable to several bacterial or viral infections. In the era of coronavirus disease 2019 (COVID-19) pandemic, it is reasonable to wonder whether DM is a risk factor for COVID-19 infection, too. It is not yet clear whether DM increases the risk for contracting COVID-19 infection or not. However, patients with DM when infected are more likely to develop severe or even fatal COVID-19 disease course than patients without DM. Certain characteristics of DM patients may also deteriorate prognosis. On the other hand, hyperglycemia per se is related to unfavorable outcomes, and the risk may be higher for COVID-19 subjects without pre-existing DM. In addition, individuals with DM may experience prolonged symptoms, need readmission, or develop complications such as mucormycosis long after recovery from COVID-19; close follow-up is hence necessary in some selected cases. We here present a narrative review of the literature in order to set light into the relationship between COVID-19 infection and DM/hyperglycemia.
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Affiliation(s)
- Evangelia Tzeravini
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | | | - Chris Siafarikas
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Anastasios Tentolouris
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Nikolaos Tentolouris
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
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16
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Bailey CJ, Gwilt M. Diabetes, Metformin and the Clinical Course of Covid-19: Outcomes, Mechanisms and Suggestions on the Therapeutic Use of Metformin. Front Pharmacol 2022; 13:784459. [PMID: 35370738 PMCID: PMC8964397 DOI: 10.3389/fphar.2022.784459] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 02/21/2022] [Indexed: 12/18/2022] Open
Abstract
Objectives: Pre-existing or new diabetes confers an adverse prognosis in people with Covid-19. We reviewed the clinical literature on clinical outcomes in metformin-treated subjects presenting with Covid-19. Methods: Structured PubMed search: metformin AND [covid (ti) OR covid-19 (ti) OR covid19 (ti) OR coronavirus (ti) OR SARS-Cov2 (ti)], supplemented with another PubMed search: "diabetes AND [covid OR covid-19 OR covid19 OR coronavirus (i) OR SARS-Cov2 (ti)]" (limited to "Clinical Study", "Clinical Trial", "Controlled Clinical Trial", "Meta-Analysis", "Observational Study", "Randomized Controlled Trial", "Systematic Review"). Results: The effects of metformin on the clinical course of Covid-19 were evaluated in retrospective analyses: most noted improved clinical outcomes amongst type 2 diabetes patients treated with metformin at the time of hospitalisation with Covid-19 infection. These outcomes include reduced admission into intensive care and reduced mortality in subgroups with versus without metformin treatment. Conclusion: The pleiotropic actions of metformin associated with lower background cardiovascular risk may mediate some of these effects, for example reductions of insulin resistance, systemic inflammation and hypercoagulability. Modulation by metformin of the cell-surface ACE2 protein (a key binding target for SARS-CoV 2 spike protein) via the AMP kinase pathway may be involved. While pre-existing metformin treatment offers potentially beneficial effects and can be continued when Covid-19 infection is not severe, reports of increased acidosis and lactic acidosis in patients with more severe Covid-19 disease remind that metformin should be withdrawn in patients with hypoxaemia or acute renal disease. Prospective study of the clinical and metabolic effects of metformin in Covid-19 is warranted.
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17
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Bradley SA, Banach M, Alvarado N, Smokovski I, Bhaskar SMM. Prevalence and impact of diabetes in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Diabetes 2022; 14:144-157. [PMID: 34939735 PMCID: PMC9060142 DOI: 10.1111/1753-0407.13243] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 11/07/2021] [Accepted: 11/26/2021] [Indexed: 12/16/2022] Open
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.
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Affiliation(s)
- Sian A. Bradley
- Global Health Neurology and Translational Neuroscience Laboratory, Sydney and Neurovascular Imaging Laboratory, Clinical Sciences StreamIngham Institute for Applied Medical ResearchSydneyNew South WalesAustralia
- University of New South Wales (UNSW)South‐Western Sydney Clinical SchoolSydneyNew South WalesAustralia
| | - Maciej Banach
- Polish Mother's Memorial Hospital Research Institute and Department of HypertensionMedical University of LodzLodzPoland
- Cardiovascular Research CentreUniversity of Zielona GóraZielona GoraPoland
| | - Negman Alvarado
- Peripheral Neurophysiology ServiceNEUROMED‐ArgentinaGodoy CruzArgentina
- Department of NeurophysiologyMendoza Medical CenterGodoy CruzArgentina
| | - Ivica Smokovski
- University Clinic of Endocrinology, Diabetes and Metabolic Disorders Skopje, Faculty of Medical SciencesUniversity Goce Delčev ŠtipŠtipNorth Macedonia
| | - Sonu M. M. Bhaskar
- Global Health Neurology and Translational Neuroscience Laboratory, Sydney and Neurovascular Imaging Laboratory, Clinical Sciences StreamIngham Institute for Applied Medical ResearchSydneyNew South WalesAustralia
- University of New South Wales (UNSW)South‐Western Sydney Clinical SchoolSydneyNew South WalesAustralia
- NSW Brain Clot BankNew South Wales Health PathologySydneyNew South WalesAustralia
- Department of Neurology and Neurophysiology, Comprehensive Stroke CenterLiverpool Hospital and South‐Western Sydney Local Health DistrictSydneyNew South WalesAustralia
- Stroke and Neurology Research GroupIngham Institute for Applied Medical ResearchLiverpoolNew South WalesAustralia
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18
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Rysz S, Jonsson Fagerlund M, Rimes‐Stigare C, Larsson E, Campoccia Jalde F, Mårtensson J. Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients. Acta Anaesthesiol Scand 2022; 66:48-55. [PMID: 34582033 PMCID: PMC8653023 DOI: 10.1111/aas.13982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 09/13/2021] [Accepted: 09/18/2021] [Indexed: 11/28/2022]
Abstract
Background Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS‐CoV‐2 positive patients. Methods In this retrospective observational study, we included 385 hospitalized SARS‐CoV‐2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS‐CoV‐2‐induced respiratory failure. Results Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS‐CoV‐2‐induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27–39.43), unknown diabetes (OR 15.86, 95% CI 4.55–55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77–53.74) was independently associated with increased risk of SARS‐CoV‐2‐induced respiratory failure. Conclusion In our cohort of hospitalized SARS‐CoV‐2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS‐CoV‐2‐associated respiratory failure.
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Affiliation(s)
- Susanne Rysz
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
- Department of Medicine Solna Karolinska Institutet Stockholm Sweden
| | - Malin Jonsson Fagerlund
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
- Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden
| | - Claire Rimes‐Stigare
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
| | - Emma Larsson
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
- Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden
| | - Francesca Campoccia Jalde
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
- Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
| | - Johan Mårtensson
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
- Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden
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19
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Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, Buse JB. COVID-19, Hyperglycemia, and New-Onset Diabetes. Diabetes Care 2021; 44:2645-2655. [PMID: 34625431 PMCID: PMC8669536 DOI: 10.2337/dc21-1318] [Citation(s) in RCA: 168] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/03/2021] [Indexed: 02/03/2023]
Abstract
Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the β-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.
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Affiliation(s)
- Kamlesh Khunti
- Diabetes Research Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, U.K.
| | - Stefano Del Prato
- Section of Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Chantal Mathieu
- Laboratory for Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Steven E Kahn
- VA Puget Sound Health Care System and University of Washington, Seattle, WA
| | - Robert A Gabbay
- Harvard Medical School, Boston, MA
- American Diabetes Association, Arlington, VA
| | - John B Buse
- Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC
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20
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Lang S, Liu Y, Qu X, Lu R, Fu W, Zhang W, Wang H, Hong T. Association between Thyroid Function and Prognosis of COVID-19: A Retrospective Observational Study. Endocr Res 2021; 46:170-177. [PMID: 34014139 DOI: 10.1080/07435800.2021.1924770] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: Coronavirus disease 2019 (COVID-19) is a severe infectious illness. It has been reported that COVID-19 has an effect on thyroid function. However, the association between thyroid function and prognosis of COVID-19 is still unclear.Methods: This retrospective study included patients with COVID-19 admitted to Tongji Hospital in Wuhan from January 28 to April 4, 2020. Demographic, epidemiological, clinical, laboratory, treatment, and outcome data were collected from patients with laboratory-confirmed COVID-19. Patients without history of thyroid disease who had a thyroid function test at admission were enrolled in the final analysis. Risk factors of in-hospital death were explored using univariable and multivariable Cox regression analyses. Survival differences were assessed with Kaplan-Meier curves and log-rank test.Results: A total of 127 patients were included in this study, with 116 survivors and 11 non-survivors. The serum levels of thyroid stimulating hormone (TSH) [0.8 (0.5-1.7) vs. 1.9 (1.0-3.1) μIU/mL, P = .031] and free triiodothyronine (FT3) [2.9 (2.8-3.1) vs. 4.2 (3.5-4.7) pmol/L, P < .001] were lower in non-survivors than in survivors, and a low FT3 state (defined as FT3 < 3.1 pmol/L) at admission accounted for a higher proportion in non-survivors than in survivors (72.7% vs. 11.2%, P < .001). Univariate Cox regression analysis showed that FT3 level (HR 0.213, 95% CI: 0.101-0.451, P < .001) and the low FT3 state (HR 14.607, 95% CI: 3.873-55.081, P < .001) were negatively and positively associated with the risk of in-hospital death, respectively. Furthermore, multivariate Cox regression analysis revealed that a low FT3 state was associated with an increased risk of in-hospital death after adjusting for confounding factors (HR 13.288, 95% CI: 1.089-162.110, P = .043). Moreover, Kaplan-Meier curves indicated a lower survival probability in COVID-19 patients with a low FT3 status.Conclusion: Serum FT3 level is lower in non-survivors among moderate-to-critical patients with COVID-19, and the low FT3 state is associated with an increased risk of in-hospital mortality of COVID-19.
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Affiliation(s)
- Shan Lang
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Ye Liu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Xue Qu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Ran Lu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Wei Fu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Wenhui Zhang
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Haining Wang
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Tianpei Hong
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
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Hirschbühl K, Dintner S, Beer M, Wylezich C, Schlegel J, Delbridge C, Borcherding L, Lippert J, Schiele S, Müller G, Moiraki D, Spring O, Wittmann M, Kling E, Braun G, Kröncke T, Claus R, Märkl B, Schaller T. Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave: A multiorgan and multimethodological approach. PLoS One 2021; 16:e0254872. [PMID: 34280238 PMCID: PMC8289110 DOI: 10.1371/journal.pone.0254872] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 07/05/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. METHODS During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. RESULTS Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. CONCLUSIONS The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.
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Affiliation(s)
- Klaus Hirschbühl
- Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Sebastian Dintner
- General Pathology and Molecular Diagnostics, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Martin Beer
- Institute of Diagnostic Virology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Claudia Wylezich
- Institute of Diagnostic Virology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Jürgen Schlegel
- Department of Neuropathology, School of Medicine, Institute of Pathology, Technical University Munich, Munich, Germany
| | - Claire Delbridge
- Department of Neuropathology, School of Medicine, Institute of Pathology, Technical University Munich, Munich, Germany
| | - Lukas Borcherding
- General Pathology and Molecular Diagnostics, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Jirina Lippert
- General Pathology and Molecular Diagnostics, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Stefan Schiele
- Computational Statistics and Data Analysis, Institute of Mathematics, University of Augsburg, Augsburg, Germany
| | - Gernot Müller
- Computational Statistics and Data Analysis, Institute of Mathematics, University of Augsburg, Augsburg, Germany
| | - Dimitra Moiraki
- General Pathology and Molecular Diagnostics, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Oliver Spring
- Anesthesiology and Operative Intensive Care Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Michael Wittmann
- Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Elisabeth Kling
- Microbiology, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Georg Braun
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany
| | - Thomas Kröncke
- Diagnostic and Interventional Radiology, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Rainer Claus
- Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Bruno Märkl
- General Pathology and Molecular Diagnostics, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Tina Schaller
- General Pathology and Molecular Diagnostics, Medical Faculty, University of Augsburg, Augsburg, Germany
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