General Information:

Id: 11,778
Diseases: COVID-19
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
review
Reference: Hussain A et al.(2020) COVID-19 and diabetes: Knowledge in progress Diabetes Res. Clin. Pract. 162 [PMID: 32278764]

Interaction Information:

Comment Diabetes and uncontrolled glycaemia were reported as significant predictors of severity and deaths in patients infected with different viruses, including the 2009 pandemic influenza A (H1N1), SARS-CoV and MERS-CoV. In the current SARS-CoV-2 pandemic, some studies did not find a clear association between diabetes and severe disease. However, other reports from China and Italy showed that older patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 and mortality.
Formal Description
Interaction-ID: 116542

affects_activity of

disease

SARS-CoV infection

Comment Diabetes and uncontrolled glycaemia were reported as significant predictors of severity and deaths in patients infected with different viruses, including the 2009 pandemic influenza A (H1N1), SARS-CoV and MERS-CoV. In the current SARS-CoV-2 pandemic, some studies did not find a clear association between diabetes and severe disease. However, other reports from China and Italy showed that older patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 and mortality.
Formal Description
Interaction-ID: 116638

affects_activity of

disease

MERS-CoV infection

Comment Diabetes and uncontrolled glycaemia were reported as significant predictors of severity and deaths in patients infected with different viruses, including the 2009 pandemic influenza A (H1N1), SARS-CoV and MERS-CoV. In the current SARS-CoV-2 pandemic, some studies did not find a clear association between diabetes and severe disease. However, other reports from China and Italy showed that older patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 and mortality.
Formal Description
Interaction-ID: 116639

affects_activity of

disease

Influenza A H1N1 infection

Comment Diabetes and uncontrolled glycaemia were reported as significant predictors of severity and deaths in patients infected with different viruses, including the 2009 pandemic influenza A (H1N1)[35], SARS-CoV and MERS-CoV. In the current SARS-CoV-2 pandemic, some studies did not find a clear association between diabetes and severe disease. However, other reports from China and Italy showed that older patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 and mortality.
Formal Description
Interaction-ID: 116641

affects_activity of

disease

COVID-19

in older patients
Comment Scarce data exist regarding glucose metabolism and development of acute complications of diabetes (e.g., ketoacidosis) in patients with COVID-19. Infection of SARS-CoV-2 in those with diabetes possibly triggers higher stress conditions, with greater release of hyperglycemic hormones, e.g., glucocorticoids and catecholamines, leading to increased blood glucose levels and abnormal glucose variability. On the otherhand, a retrospective study from Wuhan reported that around 10% of the patients with T2DM and COVID-19 suffered at least one episode of hypoglycemia (<3.9 mmol/L). Hypoglycemia has been shown to mobilize pro-inflammatory monocytes and increase platelet reactivity, contributing to a higher cardiovascular mortality in patients with diabetes. Yet it remains largely unknown how exactly the inflammatory and immune response occurs in these patients, as well as whether hyper- or hypoglycemia may alter the SARS-CoV-2 virulence, or the virus itself interferes with insulin secretion or glycemic control. Furthermore, the impact of usual diabetes drug treatment on COVID-19 outcomes, as well as therapeutic approaches for COVID-19 on glucose regulation remains unspecified.
Formal Description
Interaction-ID: 116642

affects_activity of

disease

COVID-19

Comment Several defects in immunity have been associated with hyperglycemia, even though the clinical relevance of some in vitro disturbances are still not fully understood. Poorly controlled diabetes has been linked to inhibited lymphocyte proliferative response to different kinds of stimuli, as well as impaired monocyte/macrophage and neutrophil functions. Abnormal delayed type hypersensitivity reaction and complement activation dysfunction have also been described in patients with diabetes. In vitro studies have shown that pulmonary epithelial cells exposure to high glucose concentrations significantly increases influenza virus infection and replication, indicating that hyperglycemia may enhance viral replication in vivo.
Formal Description
Interaction-ID: 116643

phenotype

hyperglycemia

increases_activity of

of influenza virus, in in vitro studies
Comment Patients with COVID-19 commonly show on admission lymphocytopenia, and to a lesser extent thrombocytopenia and leukopenia, which are more prominent among those with severe disease. Further, elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein, as well as increased coagulation activity, marked by higher d-dimer concentrations, were also associated with severity.
Formal Description
Interaction-ID: 116644

disease

COVID-19

increases_activity of

Comment Patients with COVID-19 commonly show on admission lymphocytopenia, and to a lesser extent thrombocytopenia and leukopenia, which are more prominent among those with severe disease. Further, elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein, as well as increased coagulation activity, marked by higher d-dimer concentrations, were also associated with severity.
Formal Description
Interaction-ID: 116645

disease

COVID-19

increases_activity of

phenotype

thrombocytopenia

Comment Patients with COVID-19 commonly show on admission lymphocytopenia, and to a lesser extent thrombocytopenia and leukopenia, which are more prominent among those with severe disease. Further, elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein, as well as increased coagulation activity, marked by higher d-dimer concentrations, were also associated with severity.
Formal Description
Interaction-ID: 116646

disease

COVID-19

increases_activity of

Comment Patients with COVID-19 commonly show on admission lymphocytopenia, and to a lesser extent thrombocytopenia and leukopenia, which are more prominent among those with severe disease. Further, elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein, as well as increased coagulation activity, marked by higher d-dimer concentrations, were also associated with severity.
Formal Description
Interaction-ID: 116647

disease

COVID-19

increases_quantity of

gene/protein

IL6

Drugbank entries Show/Hide entries for IL6
Comment Patients with COVID-19 commonly show on admission lymphocytopenia, and to a lesser extent thrombocytopenia and leukopenia, which are more prominent among those with severe disease. Further, elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein, as well as increased coagulation activity, marked by higher d-dimer concentrations, were also associated with severity.
Formal Description
Interaction-ID: 116648

disease

COVID-19

increases_quantity of

gene/protein

CRP

Drugbank entries Show/Hide entries for CRP
Comment Patients with COVID-19 commonly show on admission lymphocytopenia, and to a lesser extent thrombocytopenia and leukopenia, which are more prominent among those with severe disease. Further, elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein, as well as increased coagulation activity, marked by higher d-dimer concentrations, were also associated with severity.
Formal Description
Interaction-ID: 116649

disease

COVID-19

increases_activity of

Comment Viral entry into the host cells is a fundamental componen tof cross-species transmission, particularly for the coronaviruses (CoVs). Upon exposure of the host to the virus, all CoVs, through a Spike protein, bind to cells that express specific receptors. After binding to the target cells, the host-cell protease cleaves the spike, which allows the virus to enter and replicate. The angiotensin-converting enzyme 2 (ACE2) has been identified as one of the main receptors for both SARS-CoV and SARS-CoV-2.
Formal Description
Interaction-ID: 116650

environment

SARS-CoV S protein

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment Viral entry into the host cells is a fundamental componen tof cross-species transmission, particularly for the coronaviruses (CoVs). Upon exposure of the host to the virus, all CoVs, through a Spike protein, bind to cells that express specific receptors. After binding to the target cells, the host-cell protease cleaves the spike, which allows the virus to enter and replicate. The angiotensin-converting enzyme 2 (ACE2) has been identified as one of the main receptors for both SARS-CoV and SARS-CoV-2.
Formal Description
Interaction-ID: 116651

environment

SARS-CoV-2 S protein

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment A Chinese study compared 39 SARS-CoV patients without previous diabetes, who did not receive steroid treatment, with 39 matched healthy siblings and showed that 20 of the 39 SARS-CoV patients developed diabetes during hospitalization. Since immunostaining for ACE2 was strong in the pancreatic islets, it was suggested that SARS-CoV might have damaged islets and caused acute insulin dependent diabetes mellitus.
Formal Description
Interaction-ID: 116652

environment

SARS-CoV

increases_activity of

Comment Considering that ACE2 is a functional receptor for SARS-CoV-2 and its levels can be increased by ACEIs and ARBs, it has been argued that these drugs might affect negatively the outcome of COVID-19 patients. On the contrary, some have advocated that ACEIs and ARBs might rather be beneficial. SARS-CoV infection and the virus Spike protein reduce ACE2 expression. Mice injected with SARS-CoV Spike presented worsened acute lung failure, which could be attenuated by blocking the renin-angiotensin pathway. Nevertheless, a retrospective analysis performed on 112 patients with COVID-19 and CVD did not show a significant difference in the proportion of ACEI/ARB medication between survivors and non-survivors.
Formal Description
Interaction-ID: 116653

drug/chemical compound

ACE inhibitor

increases_quantity of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment Considering that ACE2 is a functional receptor for SARS-CoV-2 and its levels can be increased by ACEIs and ARBs, it has been argued that these drugs might affect negatively the outcome of COVID-19 patients. On the contrary, some have advocated that ACEIs and ARBs might rather be beneficial. SARS-CoV infection and the virus Spike protein reduce ACE2 expression. Mice injected with SARS-CoV Spike presented worsened acute lung failure, which could be attenuated by blocking the renin-angiotensin pathway. Nevertheless, a retrospective analysis performed on 112 patients with COVID-19 and CVD did not show a significant difference in the proportion of ACEI/ARB medication between survivors and non-survivors.
Formal Description
Interaction-ID: 116654

drug/chemical compound

Angiotensin II type 1 receptor blocker

increases_quantity of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment Considering that ACE2 is a functional receptor for SARS-CoV-2 and its levels can be increased by ACEIs and ARBs, it has been argued that these drugs might affect negatively the outcome of COVID-19 patients. On the contrary, some have advocated that ACEIs and ARBs might rather be beneficial. SARS-CoV infection and the virus Spike protein reduce ACE2 expression. Mice injected with SARS-CoV Spike presented worsened acute lung failure, which could be attenuated by blocking the renin-angiotensin pathway. Nevertheless, a retrospective analysis performed on 112 patients with COVID-19 and CVD did not show a significant difference in the proportion of ACEI/ARB medication between survivors and non-survivors.
Formal Description
Interaction-ID: 116655

environment

SARS-CoV

decreases_expression of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment Similar to ACEIs and ARBs, ibuprofen and thiazolidinediones can also result in increased levels of ACE2, thus generating questions regarding the safety of these drugs in patients with COVID-19.
Formal Description
Interaction-ID: 116656

drug/chemical compound

Ibuprofen

increases_quantity of

gene/protein

ACE2

Drugbank entries Show/Hide entries for Ibuprofen or ACE2
Comment Similar to ACEIs and ARBs, ibuprofen and thiazolidinediones can also result in increased levels of ACE2, thus generating questions regarding the safety of these drugs in patients with COVID-19.
Formal Description
Interaction-ID: 116657

drug/chemical compound

Thiazolidinedione

increases_quantity of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment It has been shown that dipeptidyl peptidase-4 (DPP-4) is the primary receptor of MERS-CoV. Since DPP-4 inhibitors are commonly applied in the treatment of diabetes worldwide, future research should explore whether DPP-4 may also act as receptor for SARS-CoV-2, thus contributing to a potential protective effect of these drugs against COVID-19.
Formal Description
Interaction-ID: 116658

environment

MERS-CoV

interacts (colocalizes) with

gene/protein

DPP4

Drugbank entries Show/Hide entries for DPP4
Comment It has been shown that dipeptidyl peptidase-4 (DPP-4) is the primary receptor of MERS-CoV. Since DPP-4 inhibitors are commonly applied in the treatment of diabetes worldwide, future research should explore whether DPP-4 may also act as receptor for SARS-CoV-2, thus contributing to a potential protective effect of these drugs against COVID-19.
Formal Description
Interaction-ID: 116659

drug/chemical compound

Dipeptidyl peptidase-4 inhibitor

decreases_activity of