scholarly journals Pathophysiology of COVID-19: Everywhere You Look You Will See ACE2!

2021 ◽  
Vol 8 ◽  
Author(s):  
Vladimir L. Cousin ◽  
Raphael Giraud ◽  
Karim Bendjelid
Keyword(s):  
Risk Factors ◽  
Angiotensin Converting Enzyme ◽  
Clinical Features ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Strong Link ◽  
Coagulation Abnormalities ◽  
Central Actor ◽  
Risks Factors ◽  
Relative Deficiency

Angiotensin converting enzyme 2 (ACE2) seems to be a central actor in the pathophysiology of SARS-Cov-2 infection. First, it acts as the receptor for the virus and permits its attachment to cells expressing ACE2. Second, the relative deficiency of ACE2 during infection could be linked to several clinical features encountered during the disease, like ARDS and coagulation abnormalities. This study explores the strong link between ACE2 and the majority of risk factors for the severe evolution of COVID-19. It seems that all these risks factors are linked to an increased level of ACE2 and/or imbalance in ACE/ACE2.

scholarly journals The regulation of ACE-2 in the heart and lungs

2021 ◽  
Vol 9 (40) ◽  
pp. 47-52
Author(s):  
Jonathan Kopel ◽  
Thomas Tenner ◽  
Gregory Brower
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Physiological Responses ◽  
Cardiovascular Complications ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Metabolism Regulation

The pathogenesis of SARS-CoV-2 infection or COVID-19 disease remains an active and rapidly evolving area of investigation. Currently, the angiotensin-converting enzyme 2 protein (ACE-2) is the primary receptor implicated in the pathogenesis of SARS-CoV-2. In normal physiological responses, the ACE-2 has important roles in regulating the renin-angiotensin systems (RAS) in several organs, including the heart, kidney, and lungs. Dysregulation of ACE-2 has been linked to heart failure, pulmonary hypertension, and diabetic cardiovascular complications. Two main risk factors for COVID-19 include hypertension and cardiovascular disease. However, the precise mechanism causing these risk factors for COVID-19 infectivity remains unknown. In this paper, we provide possible molecular mechanisms that underlie the cardiovascular risk factors for COVID-19. Keywords: SARS-CoV-2, COVID-19, angiotensin converting enzyme-2 (ACE-2), hormones, cardiovascular, hypoxia, metabolism, regulation, and pathophysiology

scholarly journals Angiotensin-Converting Enzyme 2 and COVID-19: Patients, Comorbidities, and Therapies

2020 ◽  
Author(s):  
Girish Pathangey ◽  
Priyal Praful Fadadu ◽  
Alexandra Raye Hospodar ◽  
Amr Abbas
Keyword(s):  
Risk Factors ◽  
Angiotensin Converting Enzyme ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Limited Evidence ◽  
Angiotensin Converting Enzyme 2 ◽  
Moderate Evidence ◽  
Receptor Blockers ◽  
Health Organization

On March 11, 2020, the World Health Organization declared COVID-19 a pandemic, and the reality of the situation has finally caught up to the widespread reach of the disease. The presentation of the disease is highly variable, ranging from asymptomatic carriers to critical COVID-19. The availability of angiotensin-converting enzyme 2 (ACE2) receptors may reportedly increase the susceptibility and/or disease progression of COVID-19. Comorbidities and risk factors have also been noted to increase COVID-19 susceptibility. In this paper, we hereby review the evidence pertaining to ACE2's relationship to common comorbidities, risk factors, and therapies associated with severe and critical COVID-19. We also highlight gaps of knowledge that require further investigation. The primary comorbidities of respiratory disease, cardiovascular disease, renal disease, diabetes, obesity, and hypertension had strong evidence. The secondary risk factors of age, sex, and genetics had limited-to-moderate evidence. The tertiary factors of ACE inhibitors and angiotensin II receptor blockers had limited-to-moderate evidence. Ibuprofen and thiazolidinediones had limited evidence.

scholarly journals Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252799
Author(s):  
Tue W. Kragstrup ◽  
Helene Søgaard Singh ◽  
Ida Grundberg ◽  
Ane Langkilde-Lauesen Nielsen ◽  
Felice Rivellese ◽  
...  
Keyword(s):  
Risk Factors ◽  
Emergency Department ◽  
Heart Disease ◽  
Longitudinal Study ◽  
Kidney Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Illness Severity ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19. Methods and results This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4–2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). Conclusion This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

scholarly journals Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

2021 ◽  
Author(s):  
Annika Lundstrom ◽  
Louise Ziegler ◽  
Sebastian Havervall ◽  
Ann-Sofie Rudberg ◽  
Fien Von Meijenfeldt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Angiotensin Converting Enzyme ◽  
Healthy Controls ◽  
Converting Enzyme ◽  
Plasminogen Activator Inhibitor 1 ◽  
Angiotensin Converting Enzyme 2 ◽  
Markers Of Inflammation ◽  
Pai 1 ◽  
D Dimer

Rationale: Angiotensin-converting enzyme 2 (ACE2) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) is unknown. Objective: To measure circulating ACE2 and ACE levels in COVID-19 patients and investigate associations with risk factors, outcome and inflammatory markers. Methods and results: Soluble ACE2 (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand factor (VWF), factor VIII (fVIII), D-dimer, interleukin 6 (IL-6), tumor necrosis factor α and plasminogen activator inhibitor 1 (PAI-1) had previously been determined. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19. sACE2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes and patients on RAS-inhibition. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 correlated with VWF, fVIII and D-dimer, while sACE correlated with IL-6, TNFα and PAI-1. Conclusions: sACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed distinctly in their correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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