Direct-acting antiviral to treat COVID-19

Press release:

An international team of scientists from the Menzies Health Institute Queensland (MHIQ) at Griffith University and from City of Hope, a research and treatment center for cancer, diabetes and other life-threatening diseases in the U.S., have developed an experimental direct-acting antiviral therapy to treat COVID-19.

Traditional antivirals reduce symptoms and help people recover earlier. Examples include Tamiflu®, zanamivir and remdesivir.

This next-generation antiviral approach used gene-silencing RNA technology called siRNA (small-interfering RNA) to attack the virus’ genome directly, which stops the virus from replicating, as well as lipid nanoparticles designed at Griffith University and City of Hope to deliver the siRNA to the lungs, the critical site of infection.

“Treatment with virus-specific siRNA reduces viral load by 99.9%. These stealth nanoparticles can be delivered to a wide range of lung cells and silence viral genes,” said co-lead researcher Nigel McMillan, Ph.D., professor and director of the Infectious Diseases & Immunology Program at MHIQ.

“Treatment with the therapy in SARS-Cov-2 infected mice improved survival and loss of disease. Remarkably, in treated survivors, no virus could be detected in the lungs,” McMillan said.

Kevin Morris, Ph.D., professor and associate director of the Center for Gene Therapy at City of Hope and co-lead researcher from both City of Hope and Griffith University said, “This treatment is designed to work on all betacoronaviruses such as the original SARS virus (SARS-CoV-1) as well as SARS-CoV-2 and any new variants that may arise in the future because it targets ultra-conserved regions in the virus’ genome.”

McMillan added, “We have also shown that these nanoparticles are stable at 4┬░C for 12 months and at room temperature for greater than one month, meaning this agent could be used in low-resource settings to treat infected patients.”

The results suggest that siRNA-nanoparticle formulations can be developed as a therapy to treat COVID-19 patients, as well as used for future coronavirus infections by targeting the virus’ genome directly.

“These nanoparticles are scalable and relatively cost-effective to produce in bulk,” Professor Morris said.

“This work was funded as an urgent call by Medical Research Futures Fund and is the type of RNA medicine that can be manufactured locally in Australia,” McMillan said.

New trial finds arthritis drug no better than standard care for severe covid-19

Adding the arthritis drug tocilizumab to standard care for patients in hospital with severe or critical covid-19 is no better than standard care alone in improving clinical outcomes at 15 days, finds a new trial published by The BMJ today.

There was an increased number of deaths at 15 days in patients receiving tocilizumab, resulting in the trial being stopped early.

Today’s results contradict earlier observational studies suggesting a benefit of tocilizumab. However, observational effects are limited by a high risk that they may be due to other unknown (confounding) factors – and some studies have not yet been peer reviewed or published in a medical journal.

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Baricitinib plus Remdesivir shows promise for treating COVID-19

This colorized transmission electron micrograph shows a SARS-CoV-2 virus particle, isolated from a patient.

Press release:

The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, reduced time to recovery for people hospitalized with COVID-19, according to clinical trial results published in the New England Journal of Medicine. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The clinical trial is the second iteration of the NIH Adaptive COVID-19 Treatment Trial (ACTT-2), a study protocol to evaluate therapeutics for people hospitalized with COVID-19. Remdesivir is a broad-spectrum antiviral treatment developed by Gilead Sciences, Inc. Baricitinib was discovered by Incyte and licensed to Eli Lilly and Company, and marketed under the brand name Olumiant. It is approved in more than 70 countries as a treatment for adults with moderately-to-severely active rheumatoid arthritis. Researchers hypothesized that because many severe symptoms of COVID-19 are caused by a poorly regulated inflammatory response, a therapeutic designed to target inflammation could be helpful for patients. The primary results of this study were first announced in September.

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Genes could be key to new COVID-19 treatments, study finds

Press release:

Potential treatments for Covid-19 have been identified after the discovery of five genes associated with the most severe form of the disease.

Genetic evidence is second only to clinical trials as a way to tell which treatments will be effective in a disease. Existing drugs that target the actions of the genes reveal which drugs should be repurposed to treat Covid-19 in clinical trials, experts say.

Genes involved in two molecular processes – antiviral immunity and lung inflammation – were pinpointed. The breakthrough will help doctors understand how Covid-19 damages lungs at a molecular level.

Researchers from the University of Edinburgh made the discovery by studying the DNA of 2,700 patients in 208 intensive care units (ICUs) in the UK.

Researchers from the GenOMICC consortium – a global collaboration to study genetics in critical illness – compared the genetic information of Covid-19 patients in ICU with samples provided by healthy volunteers from other studies, such as UK Biobank, Generation Scotland and 100,000 Genomes.

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Heart rhythm in COVID-19 patients receiving short term treatment with hydroxychloroquine

Press Release:

Sophia Antipolis, 25 September 2020: Short-term hydroxychloroquine treatment is not associated with lethal heart rhythms in patients with COVID-19 who are risk assessed prior to receiving the drug. That’s the finding of research published today in EP Europace, a journal of the European Society of Cardiology (ESC).1

“This was the largest study to assess the risk of dangerous heart rhythms (arrhythmias) in COVID-19 patients treated with hydroxychloroquine,” said study author Dr. Alessio Gasperetti of Monzino Cardiology Centre, Milan, Italy and University Hospital Zurich, Switzerland. “In our cohort, there was a low rate of arrhythmias and none were associated with hydroxychloroquine.”

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New insight into the effect of hydroxychloroquine undermines its use in COVID-19

Press release:

Researchers at Radboud university medical center have discovered an as yet unknown effect of hydroxychloroquine. It inhibits the action of a type of white blood cells important in the first line of defense against infections. Based on this research, hydroxychloroquine is unlikely to be beneficial in clearing viral infections including the new coronavirus SARS-CoV-2, they write in their publication in Cell Reports Medicine.

Hydroxychloroquine is an agent that has been used for years, originally for the treatment of malaria. It is also widely used to treat patients with rheumatic diseases, because hydroxychloroquine has immunomodulatory effects. It is not known exactly how hydroxychloroquine does this. Hydroxychloroquine use for COVID-19 remains a topic of intense debate and investigation. Especially in the context of their use as a prophylaxis, large studies are ongoing to investigate their efficacy.

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U of M trial shows hydroxychloroquine does not prevent COVID-19 in health care workers

Press release:

MINNEAPOLIS, MN-October 21, 2020 – University of Minnesota Medical School physician researchers studied hydroxychloroquine as a treatment to prevent COVID-19 for those with high-risk for exposure to the virus – health care workers.

The pre-exposure prophylaxis trial results, which were published in Clinical Infectious Diseases, determined that taking 400mg of hydroxychloroquine once or twice weekly did not prevent the development of COVID-19 in health care workers better than the placebo.

“This randomized placebo-controlled trial launched on April 6, with the objective of evaluating whether or not hydroxychloroquine taken once or twice weekly in health care workers at high risk for COVID-19 exposure could prevent COVID-19 infection,” said principal investigator Radha Rajasingham, MD, an infectious diseases physician and researcher at the U of M Medical School.

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Hydroxychloroquine linked to increased risk of cardiac arrhythmias

Press Release:

Boston, Mass. — Since the World Health Organization declared COVID-19 a Public Health Concern of Global Interest on January 30, more than one million have tested positive for the illness in the United States, and more than 62,000 have died. With no FDA-approved treatments available to date, the anti-malarial drug, hydroxychloroquine, has emerged as a potential therapy for the pneumonia associated with COVID-19, with or without the antibiotic azithromycin.

In a brief report published today in JAMA Cardiology, a team of pharmacists and clinicians at Beth Israel Deaconess Medical Center (BIDMC), part of Beth Israel Lahey Health, found evidence suggesting that patients who received hydroxychloroquine for COVID-19 were at increased risk of electrical changes to the heart and cardiac arrhythmias. The combination of hydroxychloroquine with azithromycin was linked to even greater changes compared to hydroxychloroquine alone.

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