Key China COVID-19 examination delivered results that affected ensuing exploration on Covid

Key China COVID-19 examination delivered results that affected ensuing exploration on Covid


  • Post By : Kumar Jeetendra

  • Source: University of Cincinnati

  • Date: 18 Sep,2020

Crucial China COVID-19 study produced results that Affected subsequent research on coronavirus

Early in the start of the COVID-19 pandemic, a small study in China produced results that affected subsequent research on the virus.

Researchers at the University of Cincinnati used the same research parameters on a much larger patient population and reached completely different findings. The study was published in the journal Progress in Cardiovascular Diseases in mid-July.

The primary theory that emerged from the 12-patient research 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 an essential metabolic system known as the Renin-Angiotensin-Aldosterone System (RAAS).

Henry says a lot 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, due to the disruption of RAAS, while other researchers are testing those same drugs as treatments in patients with COVID-19.

“We’re interested in trying to figure out what’s actually going on with RAAS,” Henry says. “There are a good deal of clinical trials targeting RAAS, but nobody has really examined if it is truly affected and upset in these patients. This was the focus of our investigation.”

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.”-Brandon Henry, MD, Study Co-Author, Cardiac Intensive Care Unit, Cincinnati Children’s Hospital Medical Center, University of Cincinnati

When COVID-19 first hit, anyone presenting to University of Cincinnati Medical Center with possible indicators of this virus was isolated in a separate part of the emergency department known as the”Respiratory ED.” A good deal of those people were getting blood work done, so researchers were able to pull a blood sample from those patients.

“This sets up a nice, natural experiment where all those patients are in the ED and they all have respiratory symptoms,” says Justin Benoit, MD, assistant professor at the Department of Emergency Medicine at the UC College of Medicine, who ran the logistics of this study.

“Some have COVID, some don’t, and we do not know who does or doesn’t have COVID when you are drawing the blood. Then you can begin looking for differences. Since they present likewise, when you find differences between these patient groups, you may be able to attribute that to COVID.”

Benoit says that the researchers’ aim was to attempt to find pathways that are altered in patients with COVID-19 that have specific pharmacological targets that might be used in subsequent studies.

“We were trying to inform clinical trials because there are a lot of trials being suggested or up and running at UC and at other areas, but most are based on theory and conjecture and not necessarily based on real data,” Benoit says.

Henry says they wanted to find out more about the primary 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 limits the vessels within the lung in models of people with severe respiratory distress syndrome (ARDS), according to Henry.

“The ACE2 enzyme that the virus uses takes AngII and transforms it into a different peptide called angiotensin (1-7),” says Henry. “The concept is that if the virus binds to the enzyme, its activity stops and amounts of AngII start to rise dramatically. That’s what propagates the severity of the infection and induces people to develop ARDS, or so the theory goes.”

Reducing AngII levels is also the objective of the most frequently prescribed medication in the United States, ACE inhibitors such as enalapril or lisinopril for hypertension.

The research team measured levels of the peptide in COVID-19 patients and found that AngII levels were normal. Henry says based on the results of the 12-person research in China, they expected to see AngII levels which were very high, but that wasn’t what they found in their study of 190 patients.

In a recently published follow-up study in the Journal of Medical Virology, the research team reported reduced levels of angiotensin (1-7) as compared to healthy controls.

“This is one of the first significant evidence supporting the hypothesis of a potential inhibition of ACE2 activity due to virus binding,” Henry stated.

“As angiotensin (1-7) is anti-inflammatory peptide that also dilates the vessels, low levels of the peptide due to [the coronavirus] may promote ARDS.

“We have dismantled a mountain and moved it 30 feet and reassembled it in 3 months,” she says. “Everybody stepped up, it was simply remarkable. The lab workers got things done in two days that normally take two weeks.”

Stefanie says one important element of this study is that it produced data that can hopefully help guide further research into the pathophysiology of COVID-19.

“We couldn’t replicate the data that came from China,” she says. “Our data is completely different, in the same patient population, measured at exactly the same time, measured in exactly the same laboratory technique. That little study is exactly what all of this was built from.

It’s kind of a warning or reminder that we’re doing things now in ways they have never been done before, so we need to be considerate about when data comes out, what it means and how we use it.”

Benoit says he was quite impressed by the fast reaction to the demand for COVID-19 research by the UC College of Medicine and its leadership, such as Andrew Filak, MD, the dean of the college.

The study was funded by a $50,000 grant from the UC College of Medicine Special Coronavirus Research Pilot Grant Program which was announced in early April.

In all, $425,000 was awarded to 11 jobs throughout the program that was established to quickly support the development of advanced studies that will contribute significantly to the knowledge of COVID-19 biology or pathology.

Journal reference:

Henry, B. M., et al. (2020) Circulating plasma levels of angiotensin II and aldosterone in patients with coronavirus disease 2019 (COVID-19): A preliminary report. Progress in Cardiovascular Diseases.

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