Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte

D’Onofrio, Nunzia; Scisciola, Lucia; Sardu, Celestino; Trotta, Maria Consiglia; Feo, Marisa De; Maiello, Ciro; Mascolo, Pasquale; Micco, Francesco De; Turriziani, Fabrizio; Municinò, Emilia; Monetti, Pasquale; Lombardi, Antonio; Napolitano, Maria; Marino, Federica Zito; Ronchi, Andrea; Grimaldi, Vincenzo; Hermenean, Anca; Rizzo, Maria Rosaria; Barbieri, Michelangela; Franco, Renato; Campobasso, Carlo Pietro; Napoli, Claudio; Municinò, Maurizio; Paolisso, Giuseppe; Balestrieri, Maria Luisa; Marfella, Raffaele

doi:10.1186/s12933-021-01286-7

Cited by 76 publications

(94 citation statements)

References 47 publications

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“…[32][33][34] Patients with DM have an upregulation of ACE2 expression (total and glycosylated forms) on the surface of the cells secondary to the renin-angiotensin system activation. 35 This contributes to the higher prevalence and worse prognosis of COVID-19 infection in patients with type 2 DM in conjunction with microvascular damage and overt inflammation mediated by high plasma levels of IL-6 and other pro-inflammatory cytokine. 36 Similarly, the higher binding of COVID-19 and ACE2 could explain the higher rate of hypertension among patients infected with covid-19 and their complicated course.…”

Section: Introductionmentioning

confidence: 99%

The Level of vWF Antigen and Coagulation Markers in Hospitalized Patients with Covid-19

Otair¹,

Alsaleh²,

AlQahtany³

et al. 2021

JBM

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Background:The coagulopathy of COVID-19 still awaits more clarification, and one approach that has not been investigated is to compare the hemostatic changes between COVID-19 and non-COVID-19 infected patients. Objective: This study aims to study COVID-19 coagulopathy by measuring markers of endothelial injury and coagulation, including anticoagulants (TFPI, protein C, protein S, and AT) in COVID-19 patients and compare them with non-COVID-19 patients early in the course of the disease. Methodology: This is an observational, prospective cross-sectional study comparing the levels of protein C, protein S, antithrombin (AT) III, clotting factor (F) VIII, von Willebrand factor (vWF) and coagulation screening tests (PT and a PTT), fibrinogen, D-dimer in COVID-19 patients admitted during the same time with non-COVID-19 infections. The demographic and clinical data of the patients were collected from electronic medical records during admission. Blood tests were extracted within 24 hours of admission for both groups. Results: Fifty-four (66.7% males) consecutive COVID-19 patients and 24 (59% males) non-COVID-19 controls were enrolled in the study from October 2020 till December 2020. COVID-19 patients were significantly older than non-COVID-19 (57.7±14.2 vs 50±19.8 years, p=0.005). Fibrinogen level was significantly higher in COVID-19 patients compared to controls (5.9±1.48 vs 3.9±1.57, p<0.001). There was no statistically significant difference in the level of FVIII, protein C, S, ATIII, and D-dimer between the two groups. The level of vWF Ag was statistically higher in COVID-19 patients (276.7±91.1 vs 184.7±89.4, p=0.0001). There was significant thrombocytopenia and lymphopenia among COVID-19 patients. Inflammatory markers, CRP, ferritin, and LDH, were increased in COVID-19 patients compared to non-COVID-19, but the difference was not statistically significant. High fibrinogen and vWF AG levels were the two independent variables found in COVID-19 patients. Conclusion:The level of vWF Ag is increased early in the course of COVID-19 infection. This can be used as a biomarker for endothelial injury, which is peculiar to COVID-19 infection.

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Section: Introductionmentioning

confidence: 99%

The Level of vWF Antigen and Coagulation Markers in Hospitalized Patients with Covid-19

Otair¹,

Alsaleh²,

AlQahtany³

et al. 2021

JBM

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“…It is a homotrimer with each monomer formed by 1,281 amino acids (26). This homotrimer plays a critical role in infection (22), and together with its interaction with ACE2, promotes fusion of the viral and cellular membranes allowing internalization of the virus for its intracellular replication (20,27) and causing cell viral infection mainly in the lung, where ACE2 is mainly expressed in type 2 pneumocytes (28) and causing a decrease in the number of ACE2 receptor molecules on the cell surface (15). COVID-19 had its beginning in the city of Wuhan at the end of 2019, initially appearing as a form of atypical pneumonia caused by a new type of coronavirus, classified initially as 2019-nCoV, and quickly spreading through different provinces of China and other cities of the world in <30 days, putting all health systems on alert (27).…”

Section: Sars-cov-2 and Covid-19mentioning

confidence: 99%

Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection

et al. 2022

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Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

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“…As of May 10, 2021, there have been 158,334,639 confirmed COVID-19 cases and 3,293,120 deaths worldwide (announced by World Health Organization [WHO]). Infection with SARS-CoV-2 not only leads to severe acute respiratory syndrome but also causes damage to the kidneys 2 , heart 3 , and other organs. 13.1%–14.4% of COVID-19 patients had some renal injury markers on admission, including proteinuria, hematuria, and elevated serum creatinine (SCr) and blood urea nitrogen (BUN).…”

Section: Introductionmentioning

confidence: 99%

Clinical outcomes of hospitalized COVID-19 patients with renal injury: a multi-hospital observational study from Wuhan

Chen

Liu

et al. 2021

Sci Rep

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Renal injury is common in patients with coronavirus disease 2019 (COVID‐19). We aimed to determine the relationship of estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI) with the characteristics, progression, and prognosis of COVID-19 in-patients. We retrospectively reviewed 1851 COVID-19 patients admitted to 3 hospitals in Wuhan, China. Clinical, laboratory, radiological, treatment, complication, and outcome data were analyzed. Patients were stratified according to levels of eGFR (≥ 90 vs. 60–89 vs. < 60 mL/min/1.73 m2). The risk of reaching the composite endpoint—intensive care unit admission, invasive ventilation, or death—was compared. On admission, 25.5% patients had renal impairment (eGFR < 90 mL/min/1.73 m2), but only 2.6% patients had chronic kidney disease (CKD). The overall in-hospital AKI incidence was 6.7%. Severe illness and comorbidities (hypertension, diabetes, CKD, and cardiovascular/cerebrovascular diseases) were more common among patients with low eGFR (< 90 mL/min/1.73 m2). Despite the more frequent use of intensive oxygen therapy, continuous blood purification, and glucocorticoid treatment, the prognosis of these patients was unsatisfactory, with the incidence of the composite endpoint (15.4% vs. 19.6% vs. 54.5%; P = 0.000) and complications (AKI, respiratory failure, cardiac injury, coagulation disorders, sepsis, etc.) increasing with decreasing eGFR. Kaplan–Meier survival analysis revealed that patients with eGFR < 90 mL/min/1.73 m2 or AKI had significantly escalated risks of reaching the composite endpoint. Multivariate regression analysis showed that renal insufficiency (eGFR < 60 mL/min/1.73 m2) on admission and in-hospital AKI independently predicted poor prognosis among COVID-19 in-patients. And renal impairment on admission was a greater predictor of poor prognosis in non-elderly patients than that in elderly patients. Early and continuous renal-function monitoring and early AKI diagnosis are necessary to predict and prevent the progression of COVID-19.

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Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte

Cited by 76 publications

References 47 publications

The Level of vWF Antigen and Coagulation Markers in Hospitalized Patients with Covid-19

The Level of vWF Antigen and Coagulation Markers in Hospitalized Patients with Covid-19

Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection

Clinical outcomes of hospitalized COVID-19 patients with renal injury: a multi-hospital observational study from Wuhan

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