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Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies.

ABSTRACT: On March 11, 2020, the World Health Organization declared coronavirus disease 2019 (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 the susceptibility and severity of 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 race/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.

SUBMITTER: Pathangey G

PROVIDER: S-EPMC7938645 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies.

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| S-EPMC8126690 | biostudies-literature

Increased blood angiotensin converting enzyme 2 activity in critically ill COVID-19 patients

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| S-EPMC7848790 | biostudies-literature

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID-19.

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| S-EPMC9075226 | biostudies-literature

Angiotensin converting enzyme-2 as therapeutic target in COVID-19.

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| S-EPMC7214324 | biostudies-literature

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| S-EPMC7796300 | biostudies-literature

Angiotensin Converting Enzyme 1 Polymorphisms and Lipid Profile in Mexican Patients With COVID-19.

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| S-EPMC9843789 | biostudies-literature

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers.

Project description:RationaleHypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population.ObjectiveHomozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes.Method and resultsThe Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans.ConclusionCOVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes.

| S-EPMC7478439 | biostudies-literature

COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice.

Project description:Coronavirus disease 2019 (COVID-19) is a declared pandemic that is spreading all over the world at a dreadfully fast rate. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002-2003. SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. Animal models that mimic the human disease are highly essential to develop therapeutics and vaccines against COVID-19. Here, we review transgenic mice that express human ACE2 in the airway and other epithelia and have shown to develop a rapidly lethal infection after intranasal inoculation with SARS-CoV, the pathogen of SARS. This literature review aims to present the importance of utilizing the human ACE2 transgenic mouse model to better understand the pathogenesis of COVID-19 and develop both therapeutics and vaccines.

| S-EPMC7269898 | biostudies-literature

Angiotensin-Converting-Enzyme 2 and Renin-Angiotensin System Inhibitors in COVID-19: An Update.

Project description:Ever since its outbreak, Corona Virus Disease 2019(COVID-19) caused by SARS-CoV-2 has affected more than 26 million individuals in more than 200 countries. Although the mortality rate of COVID-19 is low, but several clinical studies showed, patients with diabetes mellitus (DM) or other major complication at high risk of COVID-19 and reported more severe disease and increased fatality. The angiotensin-converting-enzyme 2 (ACE2), a component of renin-angiotensin-system (RAS); acts on ACE/Ang-II/AT1recptor axis, and regulates pathological processes like hypertension, cardiac dysfunction, Acute Respiratory Distress Syndrome (ARDS) etc. The progression of T2DM and hypertension show decreased expression and activity of ACE2. There are several treatment strategies for controlling diabetes, hypertension, etc; like ACE2 gene therapies, endogenous ACE2 activators, human recombinant ACE2 (hrACE2), Angiotensin-II receptor blockers (ARBs) and ACE inhibitors (ACEi) medications. ACE2, the receptors for SARS-CoV2, facilitates virus entry inside host cell. Clinicians are using two classes of medications for the treatment of COVID-19; one targets the SARS-CoV-2-ACE2 interaction, while other targets human immune system. The aim of this review is to discuss the role of ACE2 in diabetes and in COVID-19 and to provide an analysis of data proposing harm and benefit of RAS inhibitor treatment in COVID-19 infection as well as showing no association whatsoever. This review also highlights some candidate vaccines which are undergoing clinical trials.

| S-EPMC7908946 | biostudies-literature

Angiotensin converting enzyme 2 level and its significance in COVID-19 and other diseases patients.

Project description:BackgroundAngiotensin-converting enzyme 2 (ACE2) expressions and its modulation are of great interest as being a key receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and the protective arm of the rennin-angiotensin axis, maintaining cardiovascular homeostasis. However, ACE2 expressions and their modulation in the healthy and disease background are yet to be explored.MethodWe performed a meta-analysis, extracting the data for ACE2 expression in human subjects with various diseases, including SARS-CoV2 infection without or with co-morbidity. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Out of 203 studies, 39 met the inclusion criteria with SARS-CoV2 patients without co-morbidity, SARS-CoV2 patients with co-morbidity, cardiovascular (CVD) patients, diabetes patients, kidney disorders patients, pulmonary disease patients, and other viral infections patients.ResultsAngiotensin-converting enzyme 2 expression was significantly increased in all diseases. There was an elevated level of ACE2, especially membrane-bound ACE2, in COVID-19 patients compared to healthy controls. A statistically significant increase in ACE2 expression was observed in CVD patients and patients with other viral diseases compared to healthy subjects. Moreover, subgroup analysis of ACE2 expression as soluble and membrane-bound ACE2 revealed a remarkable increase in membrane-bound ACE2 in CVD patients, patients with viral infection compared to soluble ACE2 and pooled standard mean difference (SMD) with the random-effects model was 0.37 and 2.23 respectively.ConclusionIt was observed that utilizing the ACE2 by SARS-CoV2 for its entry and its consequence leads to several complications. So there is a need to investigate the underlying mechanism along with novel therapeutic strategies.

| S-EPMC9874405 | biostudies-literature

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