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Scientists have identified a collection of drugs with the potential to benefit tens of thousands of patients who are admitted to intensive care with life-threatening coronavirus infections.
The breakthrough emerged from a major study of critically ill patients that revealed a suite of genes involved in antiviral defences and lung inflammation that leave people at greater risk of developing severe Covid disease.
The team, led by Edinburgh University researchers, spotted five genes that raised the risk of severe illness, pointing them towards a handful of drugs that are expected to help susceptible patients. The medicines will now be prioritised for clinical trials.
“It’s absolutely startling we’ve seen these results so quickly after the start of the outbreak,” said Kenneth Baillie, a consultant in critical care medicine and senior research fellow at Edinburgh’s Roslin Institute. “What is really exciting about this is we’ve found genes that are directly therapeutically relevant. They lead us directly to treatments.”
The research, by the global Genetics of Mortality in Critical Care (GenOMICC) consortium, compared the DNA of 2,244 critically ill Covid patients from 208 UK intensive care units with the genetic make-up of healthy individuals in a control group.
The analysis revealed key differences in five genes, named IFNAR2, TYK2, OAS1, DPP9 and CCR2, which partially explained why the sick patients became critically ill. Having identified the troublesome genes, the team was able to predict what drug treatments were likely to help.
One drug that holds promise for future Covid treatment is a rheumatoid arthritis medicine called baricitinib. This reduces the activity of TYK2, which the research suggests will help reduce dangerous levels of inflammation in the lungs. Another is an antibody-based medicine that blocks CCR2 and is in clinical trials for psoriasis.
Beyond calming down the immune system, drugs may help invigorate the body’s ability to fight the virus. Some compounds are known to boost the activity of Ifnar2 and are likely to protect people from serious infections by mimicking proteins released by the immune system to fight viruses. However, these would probably need to be given early on to have a substantial impact, the scientists said.
“This is a wonderful breakthrough, really, in understanding what causes the severe disease,” said Peter Openshaw, a professor of experimental medicine at Imperial College London and a co-author on the study.
The findings have been shared with groups around the world who are running clinical trials to assess whether drugs that are already in use for other conditions can help save patients with severe Covid-19 disease. Those include the World Health Organization’s Solidarity trial, Oxford University’s Recovery trial and an international trial named Remap-Cap.
Baillie said that drugs highlighted by the research should now become the top priority for inclusion in clinical trials. “Making those choices really matters,” he said. “If we choose the right intervention to try next in clinical trials then we’ll find out that it works sooner and that could save tens of thousands of lives.” The study is published in Nature.
People with Covid-19 tend to develop symptoms as the virus multiplies in their body, but those who die often succumb to excessive lung inflammation which is driven by the immune system.
Doctors running Oxford University’s Recovery trial discovered in the summer that the cheap steroid dexamethasone slashed deaths among patients needing supplemental oxygen by up to a third, by damping down the immune system.
But more drugs are needed to help patients who do not respond to the steroid, Baillie said. “Two-thirds of them are still dying even treated with dexamethasone, so there’s a long way to go in preventing that inflammation, and we really urgently need new targets,” he said.
Source: The Guardian
Keyword: Coronavirus: UK scientists identify drugs that may help severe cases | Science