Question: what kinds of complications related to COVID-19 are associated with diabetes

Title: COVID-19 in diabetic patients: related risks and specifics of management Content: Abstract Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favor of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.

Title: COVID-19 in diabetic patients: Related risks and specifics of management Content: Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.

Title: The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms Content: Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.

Title: Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study Content: AIMS: The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. METHODS: In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. RESULTS: Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR] = 3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR = 1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. CONCLUSIONS: Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.

Title: Association of Diabetes Mellitus with Disease Severity and Prognosis in COVID-19: A Retrospective Cohort Study Content: Abstract The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.

Title: COVID-19 and diabetes: The why, the what and the how Content: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords "COVID-19" and "Diabetes" was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute ß-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.

Title: Patients with diabetes are at higher risk for severe illness from COVID-19 Content: • It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19). • We found that diabetes was associated with an approximately 4-fold increased risk of having severe/critical COVID-19 illness. • This association was independent of age, sex, obesity, hypertension and smoking. • These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.

Title: COVID-19 and diabetes: The why, the what and the how Content: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords “COVID-19” and “Diabetes” was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.

Title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis Content: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31–2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.

Title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis Content: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31-2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.

Title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics Content: BACKGROUND AND AIMS: Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. METHODS: We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: "COVID-19", "SARS-CoV-2", "diabetes", "diabetes mellitus", "SARS", "infection" and "management of diabetes mellitus" with interposition of the Boolean operator "AND". RESULTS: Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19. On the contrary, direct ß-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. CONCLUSIONS: The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with diabetes mellitus take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.

Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 μg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.

Title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.

Title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics Content: Abstract Background and aims Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. Methods We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “diabetes mellitus”, “SARS”, “infection” and “management of diabetes mellitus” with interposition of the Boolean operator “AND”. Results Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with DM contribute to poor prognosis in COVID-19. On the contrary, direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. Conclusions The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with DM take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.

Title: Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective Content: Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.

Title: Diabetes and metabolic syndrome as risk factors for COVID-19 Content: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01-01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of a dysregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.

Title: Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes Content: AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-fourCOVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P<0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4+T lymphocyte counts in severe patients were lower than those in non-severe patients (P<0.05). Logistic regression analysis identified decreased CD4+T lymphocyte counts (odds ratio [OR]=0.988, 95%Confidence interval [95%CI] 0.979-0.997) and increased SAA levels (OR=1.029, 95%CI 1.002-1.058) as risk factors for severity of COVID-19 with diabetes (P<0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4+T lymphocyte counts and high SAA levels.

Title: Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review Content: AIMS: Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to the glycemic control, and role of anti-diabetic agents in patients with diabetes. METHODS: A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. RESULTS: There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. CONCLUSIONS: Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.

Title: Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes() Content: AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-four COVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P < 0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4(+) T lymphocyte counts in severe patients were lower than those in non-severe patients (P < 0.05). Logistic regression analysis identified decreased CD4(+) T lymphocyte counts (odds ratio [OR] = 0.988, 95%Confidence interval [95%CI] 0.979–0.997) and increased SAA levels (OR = 1.029, 95%CI 1.002–1.058) as risk factors for severity of COVID-19 with diabetes (P < 0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4(+) T lymphocyte counts and high SAA levels.

Title: Diabetes and metabolic syndrome as risk factors for COVID-19 Content: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.

Title: Diabetes and COVID-19: Global and Regional Perspectives Content: The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.

Title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (pâ¯=â¯0.014), c-reactive protein (pâ¯=â¯0.008), procalcitonin (p < 0.01), and D-dimer (pâ¯=â¯0.033), and lower levels of lymphocytes (pâ¯=â¯0.032) and albumin (pâ¯=â¯0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, pâ¯=â¯0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, pâ¯=â¯0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, pâ¯=â¯0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, pâ¯=â¯0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.

Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.

Title: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Content: Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.

Title: Practical recommendations for the management of diabetes in patients with COVID-19 Content: Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.

Title: Diabetes is a risk factor for the progression and prognosis of COVID-19 Content: BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

Title: Diabetes and COVID-19: Global and Regional Perspectives Content: Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.

Title: Diabetes, Infection Risk And Covid-19 Content: Abstract Background Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial and fungal infections. The Coronavirus Disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries across the world and has claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. Scope of Review In this review, I will summarize the clinical data on the risk for infectious diseases in individuals with diabetes, highlighting the mechanisms for altered immune regulation. A special focus will be given to coronaviruses. In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end. Major Conclusions Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to design tailored treatments and clinical management of individuals affected by diabetes.

Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 µg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) ï»¿may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.

Title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations Content: Abstract Background and aims High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. Methods PubMed database and Google Scholar were searched using the key terms ‘COVID-19’, ‘SARS-CoV-2’, ‘diabetes’, ‘antidiabetic therapy’ up to April 2, 2020. Full texts of the retrieved articles were accessed. Results There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today’s times.

Title: Practical recommendations for the management of diabetes in patients with COVID-19 Content: Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.

Title: Diabetes, infection risk and COVID-19 Content: BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided. MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.

Title: Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters Content: Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.

Title: Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters. Content: Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.

Title: COVID-19 and diabetes: Knowledge in progress Content: AIMS: We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. METHODS: We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: "SARS-CoV-2", "COVID-19", "infection", "pathogenesis", "incubation period", "transmission", "clinical features", "diagnosis", "treatment", "diabetes", with interposition of the Boolean operator "AND". RESULTS: The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers or thiazolidinediones because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. CONCLUSIONS: Suggestions are made on the possible pathophysiological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.

Title: COVID 19: Diabetes and Obesity API-ICP Recommendations Content: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.

Title: COVID 19: Diabetes and Obesity API-ICP Recommendations. Content: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.

Title: COVID-19 Pandemic, Corona Viruses, and Diabetes Mellitus. Content: The pandemic of COVID-19, a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on severe acute respiratory syndrome, SARS-CoV, and Middle East respiratory syndrome, MERS-CoV, and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.

Title: COVID-19 pandemic, coronaviruses, and diabetes mellitus Content: The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.

Title: Coronavirus infection in patients with diabetes. Content: Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins. Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death. The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy. Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections. Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality. In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus; 2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes; 3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2.

Title: Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A Narrative Review Content: Abstract Aims Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to glycemic control and role of anti-diabetic agents in patients with diabetes. Methods A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. Results There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe variety of COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. Conclusions Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.

Title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature Content: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.

Title: Can We Reduce Mortality of COVID-19 if We do Better in Glucose Control? Content: The SARS-CoV-2 has infected more than 3 million people and caused more than 240,000 death globally. Among the COVID-19 patients, the prevalence of people with other chronic diseases, such as diabetes, high blood pressure, and coronary heart disease is much higher than others. More strikingly, the survival rate of diabetic patients is also much lower than in non-diabetic patients. In addition to the general damage of high glucose to cells and tissues, a recent discovery that high glucose activates interferon regulatory factor 15 promotes influenza virus -induced cytokine storm. This discovery may shed light on the high incidence of diabetes in COVID-19. Several diabetes prevention strategies together with recent significant data-driven diabetes prediction approaches, which may help COVID-19 treatments, have been proposed.

Title: Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes() Content: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.

Title: Resolviendo Una De Las Piezas Del Puzle: Covid-19 Y Diabetes Tipo 2./ [solving One of the Pieces of the Puzzle: Covid-19 and Type 2 Diabetes] Content: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the two diseases.

Title: Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication Content: OBJECTIVE: Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS: In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis. RESULTS: The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension. CONCLUSIONS: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.

Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.

Title: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Content: Abstract Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, and whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.

Title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Content: BACKGROUND: Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. METHODS: We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. RESULTS: We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity). CONCLUSIONS: Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.

Title: Diabetes and COVID-19: evidence, current status and unanswered research questions. Content: Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.

Title: Diabetes and COVID-19: evidence, current status and unanswered research questions Content: Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.

Title: Diabetes and COVID-19 : Disease-Management-People Content: The current pandemic of SARS-CoV2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.

Title: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Content: Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, but whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.

Title: Diabetes and COVID-19: Disease—Management—People Content: The current pandemic of SARS-CoV‑2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.

Title: Infección por coronavirus en pacientes con diabetes Content: Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus;2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes;3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2

Title: Issues of Cardiovascular Risk Management in People With Diabetes in the COVID-19 Era Content: People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.

Title: Issues of Cardiovascular Risk Management in People With Diabetes in the COVID-19 Era. Content: People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.

Title: Laboratory findings that predict a poor prognosis in COVID-19 patients with diabetes: A meta-analysis Content: Diabetes is one of the main comorbidities in patients infected with the SARS-CoV-2 virus, the causative agent of the new coronavirus disease 2019 (COVID-19). Because the presence of diabetes and COVID-19 in the same patient is related to a poor clinical prognosis and a high probability of death, it is necessary to determine what findings allow us to predict a good or bad resolution of the disease in order to opt for a traditional treatment or a more incisive one. In this way, in the present work we analyze which laboratory parameters showed differences in patients with COVID-19 and diabetes who recovered and in those who had complications or died.

Title: Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study Content: Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs. 31.2%), coronary heart disease (17.1% vs. 8.0%), and chronic kidney diseases (6.2% vs. 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs. 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs. 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L(-1) (interquartile range (IQR): 5.80–9.29) vs. 5.46 mmol·L(-1) (IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L(-1) (IQR: 1.67–2.76) vs. 1.75 mmol·L(-1) (IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs. 122 mmHg (IQR: 110–137), P = 0.001) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.

Title: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study Content: BACKGROUND: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. METHODS: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. RESULTS: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045). CONCLUSION: The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

Title: Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection Content: AIM: To evaluate the influence of diabetes on the severity and fatality of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The medical records of 66 hospitalized coronavirus disease 2019 (COVID-19) patients were collected and classified into non-severe (mild/moderate cases) and severe (severe/critical cases) groups. Logistic regression analysis was used to estimate the risk of severe COVID-19 (severe/critical infection). In addition, a meta-analysis including published studies reported the impact of diabetes on the severity and fatality of COVID-19. The current study was conducted using fixed effects models. RESULTS: There were 22 diabetes and 44 non-diabetes cases among the 66 hospitalized COVID-19 patients. Seven patients with diabetes (31.82%) were diagnosed as severe COVID-19 cases, which was significantly higher than that in the non-diabetes group (4/44, 9.09%, P = .033). After adjustment for age and gender, diabetes was significantly associated with COVID-19 severity (OR: 5.29, 95% CI: 1.07-26.02). A meta-analysis further confirmed the positive association between diabetes and COVID-19 severity (pooled OR = 2.58, 95% CI: 1.93-3.45). Moreover, the patients with diabetes infected with SARS-CoV-2 had a 2.95-fold higher risk of fatality compared with those patients without diabetes (95% CI: 1.93-4.53). CONCLUSIONS: Our findings provide new evidence that diabetes is associated with a higher risk of severity and fatality of COVID-19. Therefore, intensive monitoring and antidiabetic therapy should be considered in patients with diabetes with SARS-CoV-2 infection.

Title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Content: Abstract Background Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. Methods We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. Results We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37–2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09–3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74–2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%–10.9%) (after adjusting for heterogeneity). Conclusions Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.

Title: CLINICAL CHARACTERISTICS OF 28 PATIENTS WITH DIABETES AND COVID-19 IN WUHAN, CHINA. Content: Objective: Previous studies on coronavirus disease 2019 (COVID-19) were based on information from the general population. We aimed to further clarify the clinical characteristics of diabetes with COVID-19. Methods: Twenty-eight patients with diabetes and COVID-19 were enrolled from January 29, 2020, to February 10, 2020, with a final follow-up on February 22, 2020. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: The average age of the 28 patients was 68.6 ± 9.0 years. Most (75%) patients were male. Only 39.3% of the patients had a clear exposure of COVID-19. Fever (92.9%), dry cough (82.1%), and fatigue (64.3%) were the most common symptoms, followed by dyspnea (57.1%), anorexia (57.1%), diarrhea (42.9%), expectoration (25.0%), and nausea (21.4%). Fourteen patients were admitted to the intensive care unit (ICU). The hemoglobin A1c level was similar between ICU and non-ICU patients. ICU patients had a higher respiratory rate, higher levels of random blood glucose, aspartate transaminase, bilirubin, creatine, N-terminal prohormone of brain natriuretic peptide, troponin I, D-dimers, procalcitonin, C-reactive protein, ferritin, interleukin (IL)-2R, IL-6, and IL-8 than non-ICU patients. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the nonICU group. Conclusion: ICU cases showed higher rates of organ failure and mortality than non-ICU cases. The poor outcomes of patients with diabetes and COVID-19 indicated that more supervision is required in these patients. (Endocr Pract. 2020;26:xxx-xxx).

Title: Clinical Characteristics of 28 Patients with Diabetes and Covid-19 in Wuhan, China Content: Objective: Previous studies on coronavirus disease 2019 (COVID-19) were based on information from the general population. We aimed to further clarify the clinical characteristics of diabetes with COVID-19. Methods: Twenty-eight patients with diabetes and COVID-19 were enrolled from January 29, 2020, to February 10, 2020, with a final follow-up on February 22, 2020. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: The average age of the 28 patients was 68.6 ± 9.0 years. Most (75%) patients were male. Only 39.3% of the patients had a clear exposure of COVID-19. Fever (92.9%), dry cough (82.1%), and fatigue (64.3%) were the most common symptoms, followed by dyspnea (57.1%), anorexia (57.1%), diarrhea (42.9%), expectoration (25.0%), and nausea (21.4%). Fourteen patients were admitted to the intensive care unit (ICU). The hemoglobin A1c level was similar between ICU and non-ICU patients. ICU patients had a higher respiratory rate, higher levels of random blood glucose, aspartate transaminase, bilirubin, creatine, N-terminal prohormone of brain natriuretic peptide, troponin I, D-dimers, procalcitonin, C-reactive protein, ferritin, interleukin (IL)-2R, IL-6, and IL-8 than non-ICU patients. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the non-ICU group. Conclusion: ICU cases showed higher rates of organ failure and mortality than non-ICU cases. The poor outcomes of patients with diabetes and COVID-19 indicated that more supervision is required in these patients. Abbreviations: COVID-19 = coronavirus disease 2019; ICU = intensive care unit; MERS-CoV = middle East respiratory syndrome-related coronavirus; 2019- nCoV = 2019 novel coronavirus; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; SARS-CoV = severe acute respiratory syndrome-related coronavirus.

Title: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study Content: OBJECTIVE: Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS: This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS: Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and they were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS: COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

Title: Use Stones from Another Mountain to Polish One’s Jade: Learn from MERS Studies toexplore potential mechanisms underlying the effect of diabetes mellitus on COVID-19/ 中华内分泌代谢杂志 Content: Epidemiology studies suggest that comorbid diabetes may have negative impact on the progression and severity of the coronavirus disease 2019 (COVID-19), which first occurred in Wuhan. However, the exact mechanism remains unclear. A recent study on another type of coronavirus infection, Middle East Respiratory Syndrome (MERS), investigated its relationship with diabetes. This essay aims to give a brief introduction to this report and related studies, and to propose suggestions on what we can learn from these investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19.

Title: The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins? Content: An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.

Title: SGLT2 inhibition and COVID-19: The road not taken Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.

Title: SGLT2 inhibition and COVID-19: The road not taken. Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.

Title: COVID-19 and type 1 diabetes: dealing with the difficult duo Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has aroused global health concerns, particularly in relation to diabetes where it has been associated with poorer outcomes. The bulk of the evolving evidence in diabetes and COVID-19 relates to type 2 diabetes (T2D). Since there are a significant number of patients with type 1 diabetes (T1D) with unique concerns and challenges during the ongoing COVID-19 pandemic, we reviewed existing literature, relevant websites, and related guidelines to form this narrative review to help address key questions in this area. METHODS: We systematically searched the PubMed database up to May 31, 2020, and retrieved all the articles published on T1D and COVID-19. RESULTS: We found 18 relevant articles, each of which carried a part of the evidence regarding the risk of contracting COVID-19 in patients with T1D, effect of COVID-19 on development of T1D, outcomes in T1D with COVID-19, and special management issues in T1D in the light of COVID-19. These have been documented in the present review. CONCLUSION: COVID-19 with T1D presents special challenges. While the available evidence does shed some light, we need more evidence to deal with this difficult duo.

Title: COVID-19 and Diabetes: Knowledge in Progress Content: Abstract Aims We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. Methods We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: “SARS-CoV-2”, “COVID-19”, “infection”, “pathogenesis”, “incubation period”, “transmission”, “clinical features”, “diagnosis”, “treatment”, “diabetes”, with interposition of the Boolean operator “AND”. Results The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. Conclusions Suggestions are made on the possible pathological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.

Title: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Content: AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.

Title: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Content: AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10–31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th–75th percentile: 25.0–32.7) kg/m(2); with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin–angiotensin–aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA(1c), diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.

Title: COVID-19 and diabetes: What does the clinician need to know? Content: COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19.

Title: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. Content: OBJECTIVE Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

Title: Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies Content: AIMS: To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. DATA SYNTHESIS: We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged ≥60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n = 22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I2 = 41.5%) and ~threefold increased risk of in-hospital mortality (n = 15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I2 = 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias. CONCLUSIONS: Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.

Title: Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Content: OBJECTIVE Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTS The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONS C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.

Title: Diabetes Epidemiology in the COVID-19 Pandemic Content: Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.

Title: Diabetes Epidemiology in the COVID-19 Pandemic. Content: Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.

Title: Dissecting the Interaction between Coronavirus Disease 2019 and Diabetes Mellitus Content: Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Data from several countries have demonstrated higher morbidity and mortality among individuals with chronic metabolic diseases such as diabetes mellitus (DM). In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have DM, this adds another layer of complexity to their management. We explore potential interactions between anti-diabetic medications and renin-angiotensin-aldosterone-system inhibitors with COVID-19. Suggested recommendations for the use of anti-diabetic medications in COVID-19 patients with DM are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in the COVID-19 patient. In addition, we aim to increase the awareness of clinicians to the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with DM.

Title: Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature Content: The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05164-x) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.

Title: Diabetes and covid-19: more than the sum of two morbidities Content: The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.

Title: Endocrine and metabolic link to coronavirus infection Content: Type 2 diabetes mellitus and hypertension are the most common comorbidities in patients with coronavirus infections. Emerging evidence demonstrates an important direct metabolic and endocrine mechanistic link to the viral disease process. Clinicians need to ensure early and thorough metabolic control for all patients affected by COVID-19.

Title: Diabetes is a risk factor for the progression and prognosis of COVID‐19 Content: BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID‐19). METHODS: A total of 174 consecutive patients confirmed with COVID‐19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID‐19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury‐related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation‐related biomarkers such as IL‐6, C‐reactive protein, serum ferritin and coagulation index, D‐dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID‐19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID‐19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

Title: COVID‐19 and diabetes: Is there enough evidence? Content: The pandemic of COVID‐19, a disease caused by a novel coronavirus SARS‐CoV‐2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID‐19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID‐19 patients. There is only limited amount of data regarding follow‐up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID‐19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID‐19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID‐19 and its role in outcome in these patients.

Title: Diabetes and Novel Coronavirus Infection: Implications for Treatment Content: The novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) outbreak originating in December 2019 has resulted in a worldwide pandemic affecting millions across almost 200 countries. People with diabetes appear to develop more severe forms of the disease and to require intensive care unit support and/or mechanical ventilation more frequently than those with other underlying medical conditions. The mortality rate among people with diabetes is also significantly higher than that among people without diabetes. A diagnosis of diabetes is often an indicator of poor underlying metabolic health, and frequently people with diabetes have multiple risk factors for severe coronavirus disease 2019 (COVID-19), including cardiovascular and renal disease. In this review, we discuss the potential biological mechanisms by which SARS-CoV-2 may interact with disease processes implicated in diabetes and discuss how treatments commonly used for people with diabetes may affect COVID-19 severity and progression. There is currently a lack of evidence from human studies, and further trials in this area will prove useful to further expand our understanding of this rapidly developing disease process to improve outcomes for this high-risk group of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00858-2) contains supplementary material, which is available to authorized users.

Title: Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease Content: BACKGROUND: Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD. METHODS: This retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: “DM” (having DM with or without other comorbidities), “only DM” (having DM without other comorbidities), “CVD” (having CVD with or without other comorbidities), “only CVD” (having CVD without other comorbidities), and “having any comorbidity”. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities. RESULTS: Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14–2.30)) and only DM (1.69 (1.05–2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, “having any comorbidities” increased the risk of in-hospital mortality from COVID-19 (OR: 2.66 (95% CI 2.09–3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05). CONCLUSIONS: Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.

Title: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes Content: OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO(2)/FiO(2)≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.

Title: The clinical characteristics and outcomes of patients with diabetes and secondary hyperglycaemia with coronavirus disease 2019: A single-centre, retrospective, observational study in Wuhan Content: AIM: To explore whether coronavirus disease 2019 (COVID-19) patients with diabetes and secondary hyperglycaemia have different clinical characteristics and prognoses than those without significantly abnormal glucose metabolism. MATERIALS AND METHODS: We retrospectively analysed 166 COVID-19 patients at Tongji Hospital (Wuhan) from 8 February to 21 March 2020. Clinical characteristics and outcomes (as of 4 April 2020) were compared among control (group 1), secondary hyperglycaemia (group 2: no diabetes history, fasting plasma glucose levels of ≥7.0 mmol/L once and HbA1c values <6.5%) and patients with diabetes (group 3). RESULTS: Compared with group 1, groups 2 and 3 had higher rates of leukocytosis, neutrophilia, lymphocytopenia, eosinopenia and levels of hypersensitive C-reactive protein, ferritin and d-dimer (P < .05 for all). Group 2 patients had higher levels of lactate dehydrogenase, prevalence of liver dysfunction and increased interleukin-8 (IL-8) than those in group 1, and a higher prevalence of increased IL-8 was found in group 2 than in group 3 (P < .05 for all). The proportions of critical patients in groups 2 and 3 were significantly higher compared with group 1 (38.1%, 32.8% vs. 9.5%, P < .05 for both). Groups 2 and 3 had significantly longer hospital stays than group 1, which was nearly 1 week longer. The composite outcomes risks were 5.47 (1.56-19.82) and 2.61 (0.86-7.88) times greater in groups 2 and 3 than in group 1. CONCLUSIONS: Hyperglycaemia in both diabetes and secondary hyperglycaemia patients with COVID-19 may indicate poor prognoses. There were differences between patients with secondary hyperglycaemia and those with diabetes. We recommend that clinicians pay more attention to the blood glucose status of COVID-19 patients, even those not diagnosed with diabetes before admission.

Title: Influence of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 infection Content: AIMS: Diabetes mellitus is one of the most common comorbidities in Coronavirus disease 2019 (COVID‐19) patients. The objective of this study was to evaluate the influences of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 infection. MATERIALS AND METHODS: Medical records of 66 hospitalized COVID‐19 patients were collected and classified into non‐severe (mild/moderate cases) and severe (severe/critical cases) groups, respectively. Logistic regression analysis was used to estimate the risk of severe COVID‐19 (severe/critical infection). In addition, a meta‐analysis including published studies reported the impacts of diabetes mellitus on severity and fatality of COVID‐19, and our current study was conducted using fixed‐effects models. RESULTS: There were 22 diabetic and 44 non‐diabetic cases among the 66 hospitalized COVID‐19 patients. As the results shown, seven cases (31.82%) were diagnosed as severe COVID‐19 in diabetic patients, which was significantly higher than that in non‐diabetic group (4/44, 9.09%, P = 0.033). After adjustment for age and gender, the results showed that diabetes mellitus was significantly associated with COVID‐19 severity (OR: 5.29, 95% CI: 1.07–26.02). A meta‐analysis further confirmed the positive association between diabetes mellitus and COVID‐19 severity (pooled OR = 2.58, 95% CI: 1.93–3.45). Moreover, the diabetic patients infected with SARS‐CoV‐2 showed to have 2.95‐fold higher risk of fatality compared to those patients without diabetes mellitus (95% CI: 1.93–4.53). CONCLUSIONS: Our findings provide new evidences that diabetes mellitus is associated with a higher risk of severity and fatality of COVID‐19. Therefore, intensive monitoring and antidiabetic therapy should be considered in diabetic patients with SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.

Title: SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons? Content: Diabetes could be a risk factor for severity and mortality in patients with coronavirus disease 2019 COVID-19. It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but (1) lack of demonstration of SARS-CoV2 binding to DPP4 (2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV) (3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and (4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn't represent a plausible approach to mitigate COVID-19.

Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

Title: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes Content: OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO2/FiO2≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.

Title: Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: a meta-analysis of observational studies Content: Abstract Aims To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. Data synthesis We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged ≥60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n=22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I 2 =41.5%) and ∼threefold increased risk of in-hospital mortality (n=15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I 2 =46.7%). Funnel plots and Egger’s tests did not reveal any significant publication bias. Conclusions Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.

Title: Does glycemic control rescue type 2 diabetes patients from COVID-19-related deaths? Content: COVID-19 patients with diabetes are reported to have higher mortality compared with non-diabetic COVID-19 patients. However, recent investigations showed the importance of better glycemic control among diabetes patients to avoid death from COVID-19.

Title: How do we recover from COVID-19? Helping diabetes teams foresee and prepare for the psychological harms Content: The scale of the COVID-19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large-scale disasters indicates that following a first wave of admissions and deaths from COVID-19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long-term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second- and third-wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.