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Corticosteroids deemed an effective, inexpensive and safe treatment for severe COVID-19 2020-09-03
The World Health Organization released official guidance on Wednesday recommending that doctors use corticosteroids to treat “severe and critical COVID-19 patients,” a decision timed to the release of a major meta-analysis of research in JAMA showing that the anti-inflammatory drug — used to treat conditions like arthritis — is capable of reducing the mortality rate for COVID-19 patients by as much as a third.
The meta-analysis, spearheaded by the WHO, analyzed seven randomized controlled trials on dexamethasone and two other corticosteroids to measure their impact on the mortality rate of those hospitalized with COVID-19. The review included over 1,703 patients from 12 countries, 678 of whom were given corticosteroids and 1025 were given placebo or “usual care.”
Overall, the researchers found, the mortality rate was 34 percent lower among those given corticosteroids versus those who were not. “I definitely think this is a positive sign and this is good news,” Dr. James Cutrell, an associate professor of medicine at the University of Texas Southwestern’s Division of Infectious Diseases tells Yahoo Life. “I think it's good news actually on multiple fronts.”
Cutrell explains that the meta-analysis — as well as detailed results of three of the trials studied also published in JAMA today —validate what the UK-based RECOVERY trial (Randomized Evaluation of COVID-19 Therapy) first suggested in June. The RECOVERY study, which was initially criticized for being shared only via press release, also found a 30 percent reduction in the mortality rate of severely ill COVID-19 patients given dexamethasone. At the time, the authors hailed it as “groundbreaking.”
“Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result,” Peter Horby, a professor of emerging infectious diseases and global health at the University of Oxford, and the study’s lead investigator said in a June 16 press release. “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become the standard of care in these patients.”
The results, which were released a month later in the New England Journal of Medicine, virtually halted further recruitment of individuals for clinical trials of the drug, which Cutrell says is not uncommon. “Anytime evidence like that comes out, if you're doing a clinical trial where you're giving some patients steroids and you're giving some patients placebo, you have to make a decision about whether or not it's ethical to continue your trial,” Cutrell tells Yahoo Life. “Based on the RECOVERY data, [many] decided it's probably not ethical of us to continue to randomize people, to get steroids or to not get steroids.”
The meta-analysis, as a result, covered clinical trials that were already underway when the RECOVERY news broke, with patients who had been recruited from February 26 to June 9. Through careful analysis of the seven randomized controlled trials — considered the gold standard in the science world — WHO has confirmed that the mortality rate of extremely ill COVID-19 patients can be reduced with corticosteroids.
So why exactly are dexamethasone and other corticosteroids proving so effective on a virus? Cutrells says it has to do with the way the virus is affecting the body. “Our current understanding... is that when you first get infected most of the symptoms are due to the virus copying or replicating itself,” Cutrell says. For some, the infection doesn’t progress from there. But for others, in the second week or beyond, he says the illness shifts and the immune system torpedos dangerously into overdrive. “In the latter stages, a lot of the damage and death that we see is not specifically related to the virus, but it's more related to the downstream kind of unchecked inflammatory process that's going on in the body.”
This “cytokine storm,” named for hormones that help control the body’s immune response, is what often turns deadly, leading to things like Acute respiratory distress syndrome (ARDS), tissue damage and multi-organ failure. Corticosteroids, it seems, are capable of quieting down a reaction that can quickly turn deadly. “The cytokine storm is just kind of saying it's gotten out of control,” says Cutrell. “And so the steroids are kind of a blunt instrument, but it's a broad way of kind of damping down that inflammation.”
On top of aggressively targeting the immune response, another benefit of corticosteroids is that — unlike some other treatments that have been floated — they are widely accessible. “Corticosteroids are inexpensive, readily available, and based on these data, are associated with reduced mortality in critically ill patients with COVID-19,” an accompanying editorial to the JAMA study, written by Dr. Hallie C. Prescott, an assistant professor at the University of Michigan and Dr. Todd Rice, a critical care doctor and physician-scientist at Vanderbilt University Medical Center reads.
Cutrell says that corticosteroids can now “definitely” be considered a front-line defense against COVID-19, but importantly — as WHO makes clear in its guidance — should never be taken as a preventative. Instead, he hopes they’ll continue to save lives among those sickest with the virus. “This is added reassurance that [corticosteroids] are the right approach and that patients are benefiting and that we're saving lives with that,” says Cutrell. “But I think it's also good news in the sense that it shows that even in the midst of the pandemic, you can do high-quality trials and you can get the kind of answers that you need.”
Prescott and Rice agree. “The COVID-19 pandemic has brought fear and a sea of change to the world. These studies provide evidence and some hope that an effective, inexpensive, and safe treatment has been identified,” they write. “Hope because corticosteroids provide a widely available treatment for the most severely ill patients with COVID-19. But also hope from the science, by demonstration of the ability of networks to quickly launch and complete randomized trials, even during an unprecedented clinical burden.”
Although corticosteroids can benefit those with severe COVID-19, the Mayo Clinic warns of potential adverse effects associated with the drug, including elevated pressure in the eyes (glaucoma), fluid retention, high blood pressure and increased risk of other infections. As a result of these risks, WHO added to their guidance that they “suggest not to use corticosteroids in the treatment of patients with non-severe COVID-19.” Cutrell says that there’s a possibility that use of the drugs may cause a “flare up” of other infections, but that researchers will have to “watch and see” as more people are given the treatment.