BREAKING! ACE2: University Of Cincinnati Study Proves China’s Research Wrong On Virus-ACE2 Binding Effects On Renin-Angiotensin-Aldosterone System (RAAS)
ACE2: Eight months into the COVID-19 pandemic which started in Wuhan, China and spread to the rest of the world (thanks due to the incompetency of a certainHealth Organization) with disastrous effects both on the lives and economic aspects of billions of people globally with the exception of China which seems to have escaped the disastrous effects mysteriously, global researchers are now realizing that a lot of misinformation and wrong hypothesis that was fed to the world from scientist and researchers in China (deliberately or not, we are not sure) that became the backbone of wrong clinical care, research approaches and treatment protocols that were developed and used across the world so far.
However in the last few months a lot of it that originated from early research in China is now being discovered as being not true from the usage of drugs such as interferon alpha, hydrochloroquine, lopinavir / ritonavir, favipiravir, the usage of convalescent plasma to the fact that COVID-19 is just a respiratory disease to the concept of cytokine storms and many more.
In a new study by researchers from the University of Cincinnati, another misconception or wrong hypothesis that was fed to the world by Chinese researchers about how the SARS-CoV-2 coronavirus binding to the ACE2 affected the on Renin-Angiotensin-Aldosterone System (RAAS) has fortunately been finally been proven wrong and a new therapeutic mode might be developed from these new findings.
The study findings are published in the journal: Progress in Cardiovascular Diseases
https://www.sciencedirect.com/science/article/pii/S0033062020301432?via%3Dihub
In the beginning of the COVID-19 pandemic, a small study in China produced results that wrongly influenced subsequent research on the SARS-CoV-2 virus.
Fortunately researchers from the University of Cincinnati have now used the same study parameters on a much larger patient population and reached a completely different findings.
The wrong primary theory that emerged from the 12-patient study in China was that when the virus binds to the angiotensin converting enzyme 2 (ACE2), a protein on the surface of lung cells by which the virus is able to enter and infect the cell, it disrupts a vital hormonal system called the Renin-Angiotensin-Aldosterone System (RAAS).
Dr Brandon Henry, MD, with the Cardiac Intensive Care Unit at Cincinnati Children's Hospital Medical Center and co-author of the study told Thailand Medical News, "RAAS is the primary hormone system the body uses to regulate blood pressure and fluid volume status. It regulates your blood pressure, it regulates your fluids and it regulates your electrolytes."
Dr Henry said much of the debate around COVID-19 research has been on the potential for danger from certain drugs, such as ACE inhibitors and angiotensin receptor blockers, because of the disruption of RAAS, while other researchers are testing those same drugs as therapies in patients with COVID-19.
He added, "We were interested in trying to figure out what's actually going on with RAAS. There are a lot of clinical trials t
argeting RAAS, but no one has really examined if it is truly affected and disturbed in these patients. That was the focus of our investigation."
During the time when COVID-19 first hit the United States, anyone presenting to University of Cincinnati Medical Center with potential symptoms of the virus was isolated in a separate part of the emergency department called the "Respiratory ED." A lot of those people were getting blood work done, so researchers were able to pull a blood sample from those patients.
Dr Justin Benoit, MD, assistant professor in the Department of Emergency Medicine at the UC College of Medicine, who ran the logistics of the study commented, "This sets up a nice, natural experiment where all these patients are in the ED and they all have respiratory symptoms. Some have COVID, some do not, and we don't know who does or doesn't have COVID when you're drawing the blood. Then you can start looking for differences. Since they all present similarly, when you find differences between these patient groups, you might be able to attribute that to COVID."
Dr Benoit said the study teams' goal was to try to find pathways that are altered in patients with COVID-19 that have specific pharmacological targets that could be used in subsequent studies.
He added, "We were trying to inform clinical trials because there are a lot of trials being proposed or up and running at University of Cincinnati and in other places, but most are based on theory and conjecture and not necessarily based on actual data.”
The study team said they wanted to learn more about the main hypothesis on how COVID-19 causes severe disease in some patients. The enzyme called ACE2 breaks down a peptide called angiotensin II (AngII), which causes inflammation and restricts the vessels within the lung in models of people with acute respiratory distress syndrome (ARDS).
Dr Henry added, "The ACE2 enzyme that the virus uses takes AngII and converts it into another peptide called angiotensin (1-7). The idea is that when the virus binds to the enzyme, its activity stops and levels of AngII start to rise dramatically. That's what propagates the severity of the infection and causes people to develop ARDS, or so the theory goes."
Hence reducing AngII levels was also the goal of the most commonly prescribed medication in the United States, ACE inhibitors such as enalapril or lisinopril for hypertension.
The study team measured levels of this peptide in COVID-19 patients and discovered that AngII levels were normal.
Dr Henry said that basing on the results of the 12-person study in China, they expected to see AngII levels that were very high, but that was not what they found in their study of 190 patients.
Importantly in a recently published follow-up study in the Journal of Medical Virology, the research team reported
low levels of angiotensin (1-7) as compared to healthy controls.
https://onlinelibrary.wiley.com/doi/10.1002/jmv.26479
Dr Henry further added, "This is among the first substantial evidence supporting the hypothesis of a potential inhibition of ACE2 activity due to virus binding.
As angiotensin (1-7) is anti-inflammatory peptide that also dilates the vessels, low levels of this peptide due to the coronavirus, may promote ARDS. As such, supplementation with synthetic angiotensin (1-7) may be a potential therapeutic target for treating COVID-19."
In addition, the blood samples collected in the University of Cincinnati Medical Center Emergency Department were analyzed by the lab run by Stefanie Benoit, MD, in the Division of Nephrology and Hypertension, wife of Justin, and co-author of the study. She says the speed at which this trial got up and running is unprecedented.
She added, "We have dismantled a mountain and moved it 30 feet and reassembled it in three months. Everybody stepped up, it was just amazing. The lab workers got things done in two days that normally take two weeks."
Dr Stefanie says one important aspect of this study is that it produced data that can hopefully help guide further research into the pathophysiology of COVID-19.
She said, "We could not reproduce the data that came out of China. Our data is completely different, in the same patient population, measured at the same time, measured in the same laboratory technique. That small study is what all of this was built off of. It's kind of a warning or reminder that we are doing things now in ways they've never been done before, so we have to be thoughtful about when data comes out, what it means and how we use it."
Dr Benoit says he was very impressed by the fast response to the need for COVID-19 research by the University Of Cincinnati College Of Medicine and its leadership, including Dr Andrew Filak, MD, the dean of the college.
The new research findings has now set many other global researchers and healthcare professionals into a new state of frenzy as for a few months now they were basing a lot of research and treatment protocols on the wrong hypothesis that originated from China once again.
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