Association of Circulating ACE2 Levels With COVID-19

Study Overview
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Brief Summary
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COVID-19 cases are rising substantially in Jordan. Since this is a novel virus, there is still much to be investigated surrounding its pathophysiology in order to attempt to find suitable treatments or better decision-making in the prognosis of the disease. This project aims to identify if soluble angiotensin-converting enzyme (ACE2) can be used as a prognostic factor for COVID-19 severity, which will allow clinicians to manage COVID-19 cases more efficiently. ACE2 is of interest since the coronavirus enters host cells through ACE2 receptors. It can slo be hypothesized that the irus may also bind to soluble ACE2, but without mediating its effects. It si, therefore, expected that those with higher levels of ACE2 would more likely have milder disease. This can potentially help improve survival rate, allowing clinicians to identify the higher-risk patients and monitoring them more closely.

Detailed Description
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SARS-CoV-2 is a new isolate of coronavirus that caused an epidemic in Wuhan, China in December 2019. The virus has then spread to the rest of the world causing a pandemic, and the disease the virus causes was designated the name COVID-19. The presence of underlying medical condition increases a risk of severe disease course. Diabetes and cardiovascular disease are amongst the conditions that are associated with the worst COVID-19 prognosis . Renal failure is also associated with more severe illness On another note, angiotensin-converting enzyme 2 (ACE2) is expressed in human airway epithelia, lung parenchyma, small intestine cells as well as in the heart, kidneys and testis It functions as both an enzyme and a receptor for viral entry as it is known that SARS-CoV-2 enters into human host cells mainly through the cellular receptor ACE2, . It is hypothesized that with the damage and loss of cells induced by infection, enzymatic ACE2 activity would be globally compromised, inducing a state of relative ACE2 deficiency. This leads to enhanced and protracted tissue and vessel exposure to Ang II and therefore vasoconstriction, enhanced thrombosis, increased tissue permeability and cytokine production resulting in inflammation Chronic angiotensin 1 receptor (AT1R) blockade elevates ACE2 expression . Unlike ACE1, however, ACE2 is insensitive to the actions mediated by ACE inhibitors . It might be appealing to propose that chronic use of ACE inhibitors or AT1R antagonists puts patients at particular high risk if they get infected with SARS-CoV-2, as ACE2 overexpression may facilitate viral replication in the lung tissue . However, results of some studies performed in healthy human subjects did not confirm such results. In vitro studies, on the other hand, depict reduced concentrations of soluble ACE2 despite the increase in membrane expression and tissue levels. Therefore, there is no current significant evidence regarding the effects of ACE inhibitors and ARBs on COVID-19 infection . In contrast, mild or moderate ACE2 deficiency is unlikely to be protective from viral invasion either. This is due to the intrinsically high affinity of SARS-CoV-2 to ACE2 receptors The soluble form of ACE2 may be a biomarker of severity of COVID-19 progression in patients . This could be due to the fact that COVID-19 binds to the soluble form, leaving less to be bound to the ACE2 receptor and be taken up by host cells The aim of this project is to identify any association between ACE2 levels with severity of COVID-19.

Official Title
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Association of Circulating ACE2 Levels With COVID-19

Conditions
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COVID-19, COVID-19 Respiratory Infection

Intervention / Treatment
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* Diagnostic Test: ACE serum levels


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 and above Gender: both males and females. Confirmed diagnosis of COVID-19 for patients and confirmed absence of COVID-19 Exclusion Criteria: Healthy individuals: not being diagnosed with COVID-19 or at least has not been in close contact with a person diagnosed with COVID-19.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Covid-19 Patients<br>Blood sample from admitted patients will be drawn | Diagnostic Test: ACE serum levels<br>* Circulating ACE2 level will be measured<br>|
| Control Patients<br>Blood sample from control group will be drawn | Diagnostic Test: ACE serum levels<br>* Circulating ACE2 level will be measured<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACE2 level | Serum level of ACE2 in control and COVID 19 patients will be measured | 3 months |