A type of arthritis drug may reduce the risk of dying for elderly patients with COVID-19.
We urgently need to find more effective treatments for COVID-19 while we wait for a vaccine to become widely available Professor Justin Stebbing Study author
In the early-stage study, 83 patients, with a median age of 81 and all suffering from moderate to severe COVID-19 infection, were given a drug called baricitinib. This medication is usually used to treat rheumatoid arthritis, and was initially identified by the Imperial team using artificial intelligence as a drug that could have anti-viral and anti-inflammatory effects.
In the study, the patients, who were in multiple hospitals across Italy and Spain, had a 71 per cent reduced risk of dying compared to patients who had not taken the drug. The study also found that 17 per cent of patients who were given the drug died or needed to go on a ventilator, compared to 35 per cent in the control group who were not given the medication.
The research team say the findings are being followed up with large-scale clinical trials.
AI first identified drug
Professor Justin Stebbing, co-lead author of the study from the Department of Surgery and Cancer at Imperial said: “We urgently need to find more effective treatments for COVID-19 while we wait for a vaccine to become widely available. This is one of the first COVID-19 treatments to go from computer to clinic and laboratory. It was first identified by an AI algorithm in February, which scanned thousands of potential drugs that could work against this virus.
“The study suggests this drug can aid recovery of patients with moderate to severe COVID-19, and may provide a new weapon in our arsenal against the virus. Large-scale clinical trials of this drug, to further investigate its potential, are now under way”
In the research, scientists from the Karolinska Institutet in Sweden together with the Imperial team grew miniature human organs in the lab, called organoids, to investigate how exactly the drug may combat COVID-19.
The findings revealed that the drug may help work in two ways: reduce organ damage caused by inflammation, and blocking the virus entering human cells.
Drug blocks virus invading cells
When infected with the COVID-19 virus, called SARS-CoV-2, the body releases different types of inflammatory molecules, called chemokines and cytokines. These molecules act as the early warning system for the body, telling the immune system the body is under attack.
This study has also shone a light on exactly how this drug may protect us at the cellular level. Professor Volker Lauschke Study author
However, in the case of COVID-19, particular cytokine and chemokines, including those called interleukins and interferons, causes this warning system to spiral out of control, and trigger a so-called cytokine storm.
This cytokine storm not only causes significant damage to the body’s organs, but the study revealed it also helps the virus gain access inside human cells.
The study showed a particular cytokine, called an interferon, increases the number of receptors, or docking points, for the virus. By doing this it, in effect, lowers the drawbridge and lets the virus into the cells of the body.
The researchers revealed the drug blocks this process occurring and so increases survival from COVID-19. The research also suggested COVID-19 increases the activity of genes related to platelets, which can make the blood sticky and more likely to form clots. The drug baricitinib was shown to reduce the activity of the genes.
Study confirms earlier patient reports
Professor Volker Lauschke, co-lead author from Karolinska Institutet in Sweden, explained: “This study confirms what AI predicted, and what we were hearing from patient case reports. For instance one case involved an 87-year-old severely unwell patient from Foggia, Italy, who showed rapid improvement after being given the drug, whereas her husband and son, who did not receive baricitinib, died. This study has also shone a light on exactly how this drug may protect us at the cellular level. This helps us understand why other types of drugs are proving beneficial, or not beneficial, as we as help identify other treatments which may tackle COVID-19.”
Professor Stebbing added: “We have seen the top line results of a randomized study called the Adaptive Covid Treatment Trial-2 announced recently, showing benefits of baricitinib plus remdesevir, compared to remdesvir alone in over one thousand patients. Other very large trials occurring now include COV-BARRIER, and this will help create a fuller picture of the benefits and side effects of the oral medication (a small number of the patients in our study needed to stop the treatment due to problems with liver function). Further trials comparing baricitinib to other drugs in COVID-19 patients would also be helpful in improving outcomes.”
'JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality' is published in the journal Science Advances
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