Excess Mortality in COVID-19-Positive Versus COVID-19-Negative Inpatients With Diabetes: A Nationwide Study

Spanakis, Elias K.; Yoo, Ashley; Ajayi, Oluwagbemiga; Siddiqui, Tariq; Khan, Mohd Washid; Seliger, Stephen L.; Klonoff, David C.; Feng, Zhaoyong; Sorkin, John D.

doi:10.2337/dc20-2350

Cited by 9 publications

(8 citation statements)

References 4 publications

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“…Type 2 diabetes mellitus (T2DM) has been established as the most important risk factor for SARS-CoV-2 infection [ 89 , 90 ]. T2DM is a heterogeneous disease characterized by elevated levels of blood glucose as a result of peripheral insulin resistance (IR), which is the impaired ability of target tissues to sense or respond to insulin stimulation, together with varying degrees of deficient insulin secretion by pancreatic islet β cells (β cell dysfunction) [ 91 ].…”

Section: Resultsmentioning

confidence: 99%

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

et al. 2022

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DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, and the immune system, among others. It has recently acquired an especial relevance due to the possibility to act as a receptor or co-receptor for SARS-CoV-2, as it has been already demonstrated for other coronaviruses. In this review, we analyze the evidence for the role of DPP4 on COVID-19 risk and clinical outcome, and its contribution to COVID-19 physiopathology. Due to the pathogenetic links between COVID-19 and diabetes mellitus and the hyperinflammatory response, with the hallmark cytokine storm developed very often during the disease, we dive deep into the functions of DPP4 on carbohydrate metabolism and immune system regulation. We show that the broad spectrum of functions regulated by DPP4 is performed both as a protease enzyme, as well as an interacting partner of other molecules on the cell surface. In addition, we provide an update of the DPP4 inhibitors approved by the EMA and/or the FDA, together with the newfangled approval of generic drugs (in 2021 and 2022). This review will also cover the effects of DPP4 inhibitors (i.e., gliptins) on the progression of SARS-CoV-2 infection, showing the role of DPP4 in this disturbing disease.

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Section: Resultsmentioning

confidence: 99%

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

et al. 2022

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“…The most common co-morbidities in our cohort were hypertension (70.6%) and diabetes mellitus (52.9%). Diabetes is a known risk factor for death in COVID-1916 and the crude mortality rate for hospitalized patients with diabetes was 25.2% 16. One study showed that 49% ICU COVID-19 patients had hypertension 17.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes is a known risk factor for death in COVID-19 16 and the crude mortality rate for hospitalized patients with diabetes was 25.2%. 16 One study showed that 49% ICU COVID-19 patients had hypertension. 17 As we expected, young patients (below 67 y old) lived longer after onset of symptoms than older patients, which is consistent with the literature showing that old patients had higher mortality rate.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Inflammatory Cell Infiltration and Expression of STAT6 in the Lungs of Patients With COVID-19: An Autopsy Study

Cao

Birkenbach²,

Chen³

2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Background: Severe acute respiratory syndrome coronavirus 2 causes diffuse alveolar damage (DAD), lymphocyte infiltration in the lungs and a cytokine storm. In this study we examined inflammatory cell infiltrates and the expression of signal transducer and activator of transcription (STAT) 6 in the lungs of patients with coronavirus disease 2019 (COVID-19).Methods: Eighteen COVID-19 autopsy cases, 9 non-COVID cases with DAD, and 11 controls without lung diseases were included. Immunostainings for STAT6, CD3, CD4, CD8, CD68, and broad-spectrum keratins were performed. Results:The average age of COVID-19 patients was 64.4 ± 2.1 years. The disease duration was 7 to 53 days. The number of pneumocytes, macrophages or CD3 + T cells was significantly increased in the lungs of patients with COVID-19. Patients' age above 67 years, blood troponin levels > 0.2 ng/mL, platelet count > 100×10 9 /L, lung macrophages > 130/high-power field (HPF), CD3 + T cells > 145/HPF, CD8 + T cells <30/HPF, and CD8/CD4 ratio <1 were associated with shorter survival duration after onset of symptoms. In addition, STAT6 staining was much stronger in pneumocytes and lymphocytes in the lungs of patients with COVID-19 than non-COVID DAD patients or controls. Conclusion:Older age, high blood troponin level and platelet count, more macrophages and fewer CD8 + T cells in the lungs of COVID-19 were associated with poorer outcome. STAT6 expression was increased in pneumocytes and lymphocytes in the lungs of patients with COVID-19, implying a role of STAT6 in cytokine storms.

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“… 19 , 20 In a study of inpatients with diabetes ( n = 6014), those with COVID-19 infection were 3.6 times more likely to die than those without COVID-19. 21 There have also been reports indicating that COVID-19 increases the risk of new-onset type 2 diabetes mellitus (T2DM), 22 and corticosteroid therapy used in the treatment of severe COVID-19 infection was associated with the development of DKA in patients with T2DM, especially in poorly controlled individuals. 23 …”

Section: Collision Of Two Pandemicsmentioning

confidence: 99%

COVID-19 and the hidden threat of diabetic microvascular complications

Zaghloul

Malik

2022

Therapeutic Advances in Endocrinology

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The coronavirus disease 2019 (COVID-19) pandemic affected at least 200 million individuals worldwide and resulted in nearly 5 million deaths as of October 2021. According to the latest data from the International Diabetes Federation (IDF) in 2021, the diabetes pandemic has affected 537 million people and is associated with 6.7 million deaths. Given the high prevalence of both diabetes and COVID-19 and common pathological outcomes, a bidirectional relationship could have a catastrophic outcome. The increased risk of COVID-19 in those with obesity and diabetes and higher morbidity and mortality has received considerable attention. However, little attention has been given to the relationship between COVID-19 and microvascular complications. Indeed, microvascular complications are associated with an increased risk of cardiovascular disease (CVD) and mortality in diabetes. This review assesses the evidence for an association between diabetic microvascular complications (neuropathy, nephropathy, and retinopathy) and COVID-19. It draws parallels between the pathological changes occurring in the microvasculature in both diseases and assesses whether microvascular disease is a prognostic factor for COVID-19 outcomes in diabetes.

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Excess Mortality in COVID-19-Positive Versus COVID-19-Negative Inpatients With Diabetes: A Nationwide Study

Cited by 9 publications

References 4 publications

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

Patterns of Inflammatory Cell Infiltration and Expression of STAT6 in the Lungs of Patients With COVID-19: An Autopsy Study

COVID-19 and the hidden threat of diabetic microvascular complications

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