Dexamethasone – the first effective treatment
In a press release dated June 16th 2020 – researchers from the RECOVERY trial at Oxford, announced the results of a randomized control trial in which severely ill patients were given dexamethasone, an anti-inflammatory of the glucocorticoid family. The sickest of those patients who were on ventilators saw a decline in death of one third. In less such patients, those on oxygen therapy but not on ventilators mortality declined by 20%. Of note patients who were neither ventilated nor on oxygen showed no such decreases.
Richard Haynes from the University of Oxford, one of the leaders of the RECOVERY trial, wrote to the Scientist saying: “We tested it because we believed it could be effective, but I don’t think anyone was expecting to see quite such large effects.”
While there are those who say that it is too early to make a definitive conclusion many hospitals in US states are adding dexamethasone The benefits of the drug include the fact that it is a well known drug, cheap and widely available. Additionally the fact that it is generally safe, well-tolerated and has a long-half life – thus allowing once a day dosage – makes it a particularly good candidate. It also “makes sense” that it should work by decreasing the inflammatory and white blood cell response to the lungs.
In the UK, the chief medical officers of England, Wales, Scotland, and Northern Ireland wrote to all the doctors and hospitals to indicate that dexamethasone should become standard care for admitted patients with COVID-19 who require oxygen.
“It’s a very safe, generally well-tolerated–at reasonable doses–steroid that works predominantly by its anti-inflammatory effects,” said Dr. Matthew Cheng, a microbiologist and infectious disease expert at the McGill University Health Centre. “With regards to the press release, I was quite honestly elated. This is the first data that we have that suggests that a drug is able to improve the chances of survival in those that are critically ill, and so while I eagerly await the scientific publication I was absolutely thrilled to receive the news and to read about it yesterday,” he added.
How does dexamethasone work?
Dexamethasone, a glucocorticoid and other similar drugs regulate the body’s immune system and response by entering a cell’s nucleus and suppressing expression of genes that encode inflammatory cytokines and increasing expression of other genes that have been shown to limit immune system overreactions.
ARDS is a syndrome with different causes, including pneumonia, sepsis, and inhalation injuries. Symptoms include shortness of breath, faster respiratory and heart rates, and dangerously low blood oxygen levels. According to Rochwerg, ARDS is inflammation-driven, so the problem is actually the intensity of the immune response, rather than the trigger itself. In ARDS, the body produces inflammatory cytokines, and white blood cells go into the alveoli of the lungs, potentially causing inflammation.
“COVID–in the extreme case–an cause ARDS, and that’s why people die predominantly,” Rochwerg says. People are sick for weeks upon weeks, by which time the virus might have cleared out of their systems, he explains, “but it’s their own bodies’ ramped-up inflammatory process that’s now caused all the damage in the lungs. Based on that idea, it makes sense that steroids should work. They help dampen the host response. They help knock down those inflammatory cytokines and all those white blood cells going to the lungs.”
While very promising in the sickest of patients the mortality rate still remained high and further trials and understanding is needed to improve outcome in both the sickest of patients as those who are less severely ill. More research is required with new drugs and strategies required to further decrease death and the severity of disease.