Remdesivir slows COVID-19 progression in macaques: Study

Agencies
June 10, 2020

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

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News Network
February 21,2020

Washington, Feb 21: The fat around arteries may play an important role in keeping the blood vessels healthy, according to a study in rats that may affect how researchers test for treatments related to plaque buildup, as seen in conditions leading to heart attack.

The study, published in the journal Scientific Reports, noted that the fat, known as perivascular adipose tissue, or PVAT, helps arteries let go of muscular tension while under constant strain.

According to the researchers, including Stephanie W. Watts from the Michigan State University in the US, this feature is similar to how the bladder expands to accommodate more liquid, while at the same time keeping it from spilling out.

"In our study, PVAT reduced the tension that blood vessels experience when stretched," Watts said.

"And that's a good thing, because the vessel then expends less energy. It's not under as much stress," she added.

According to Watts and her team, PVAT has largely been ignored by researchers believing its main job was to store lipids and do little more.

Until now, she said, scientists only divided blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media, and the outermost layer called the tunica adventitia.

Watts believes PVAT is the fourth layer, which others have called tunica adiposa.

Tunica, she said, meant a membranous sheath enveloping or lining an organ, and adiposa is a synonym for fat.

"For years, we ignored this layer -- in the lab it was thrown out. In the clinic it wasn't imaged. But now we're discovering it may be integral to our blood vessels," Watts said.

"Our finding redefines what the functional blood vessels are, and is part of what can be dysfunctional in diseases that afflict us, including hypertension. We need to pay attention to this layer of a blood vessel because it does far more than we originally thought," she added.

Earlier studies, Watts said, had shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

In the current study, the researchers decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

They tested the thoracic aorta in rats, and found those with intact PVAT had more stress relaxation than those without.

The study revealed that the pieces of artery with surrounding fat had measurably relaxed more than those without.

Watts and her colleagues then tested other arteries, and were able to duplicate the same response.

"It's not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it's a general phenomenon," she said.

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Agencies
May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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Agencies
March 27,2020

New Delhi, Mar 27: The Centre has restricted sale and distribution of "hydroxychloroquine" declaring it as an essential drug to treat the COVID-19 patients and meet the requirements of emergency arising due to the pandemic.

The Ministry of Health and Family Welfare on Thursday made the announcement making it clear that the order "shall come into force on the date of its publication in the official Gazette".

In the order, the government declared that the Central government is "satisfied that the drug hydroxychloroquine is essential to meet the requirements of emergency arising due to pandemic COVID-19 and in the public interest, it is necessary and expedient to regulate and restrict the sale and distribution of the drug 'hydroxychloroquine' and preparation based thereon for preventing their misuse".

"Now, therefore, in exercise of the powers conferred by Section 26B of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central government hereby directs that sale by retail of any preparation containing the drug Hydroxychloroquine shall be in accordance with the conditions for sale of drugs specified in Schedule H1 to the Drugs and Cosmetics Rules, 1945."

The order came at a time when the novel coronavirus claimed 16 lives and infected over 600 people across India.

The announcement regarding ban of sale and distribution of the drug was made by the government earlier but it issued an official Gazette notification on Thursday signalling that hydroxychloroquine -- an anti-Malaria drug -- will work as a medicine for treating coronavirus infected patients as well.

Recently, the national task force for COVID-19 constituted by Indian Council for Medical Research (ICMR) has recommended hydroxy-chloroquine as a preventive medication.

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