An inexpensive and widely available steroid used since the early 1960s and known for its anti-inflammatory properties is being touted as the next life-saving treatment for COVID-19 — but it’s not the miracle cure people have been hoping for. It’s called dexamethasone, and is one of several drugs tested in the world’s largest trial of existing treatments to see which might be effective on the novel coronavirus. This morning, the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, led by the University of Oxford, released preliminary findings that indicate that the drug may be able to cut the risk of death by one-third for COVID patients on ventilators, and by one-fifth for those on oxygen. But medical experts are encouraging the public to remain cautious about the results of the trial — at least until there is a published, peer-reviewed article providing more details about the study. So what exactly is dexamethasone, and how can it help treat COVID-19? Here’s what you need to know.
What is dexamethasone?
Dexamethasone is a corticosteroid (cortisone-like medicine or steroid) used as an anti-inflammatory drug on a variety of conditions including asthma, arthritis, multiple sclerosis, and severe allergies, according to the Mayo Clinic. Early in the pandemic, it was clear to medical experts like Dr. Charles Powell that inflammation and immune responses to the novel coronavirus — not the virus itself — caused moderate-to-severe lung disease in COVID-19 patients. Powell — the chief of the division of pulmonary, critical care, and sleep medicine at the Mount Sinai Health System and the CEO of the Mount Sinai-National Jewish Health Respiratory Institute — tells Rolling Stone that the early cases in Wuhan indicated a potential role for steroids in treating patients with moderate to severe lung involvement.
Also, dexamethasone is cheap and already available globally. The dosage used to treat COVID-19 costs approximately $6.79 per day, so typically around $44.00 for the course of treatment required for one person, the BBC reports.
What were the findings of the RECOVERY trial?
More than 11,500 patients from about 175 hospitals in the U.K. are part of the trial. It has several arms, each designed to test whether several existing drugs — including dexamethasone — could be effective in treating COVID-19. Of those patients, 2,104 were randomly assigned to take dexamethasone. Compared with the 4,321 patients in the trial assigned to receive typical COVID care alone (meaning, none of the treatments being tested), those who took dexamethasone for 10 days saw a one-third reduction in deaths in ventilated patients, and a one-fifth reduction in patients that required oxygen.
“These preliminary results from the RECOVERY trial are very clear — dexamethasone reduces the risk of death among patients with severe respiratory complications,” Dr. Martin Landray, professor of medicine and epidemiology at the University of Oxford, and one of the study’s chief investigators said in a statement. “COVID-19 is a global disease — it is fantastic that the first treatment demonstrated to reduce mortality is one that is instantly available and affordable worldwide.”
How would it treat COVID-19?
When it comes to treating viral pneumonia — like the kind caused by the novel coronavirus — two types of drugs have the potential to help: antivirals and anti-inflammatory medications, says Dr. Charles S. Dela Cruz, a pulmonologist and associate professor at the Yale School of Medicine. Antivirals like remdesivir slow down the growth and replication of the virus. Anti-inflammatory drugs, including steroids like dexamethasone, help suppress on overblown immune response.
“It mimics naturally occurring things within our body that tell our immune response to slow down,” says Dr. Dean Hart, a New York City-based microbiologist with expertise in the transmission of viruses and diseases. “When it comes to COVID, there are definitely some people that die because of a hyper-immunological reaction,” he explains. “The virus is being killed off, but then all these other things occur, and the secondary effect from having this bat virus in your body is that it creates a freaky immune response.”
The result is a Catch-22 situation. “On the one hand, you want to dampen the immune response to prevent the potential damage, but we know that your immune system is really important to fight the virus,” Dela Cruz tells Rolling Stone. “It’s almost like the Goldilocks rule: Too much is bad, too little is bad, so we’ve tried to find the right balance.” Complicating matters further, some research has indicated that the combination of pneumonia and steroids could increase the risk of death in some patients. And according to Dela Cruz, trials conducted during the SARS and MERS outbreaks didn’t show any significant benefits from using steroids. “So now, we’re faced with a pandemic — a new virus, causing a lot of disease,” he explains. “And then the question is, what do we do with steroids?”
What are the potential side effects?
Though at this point it’s unclear what kinds of side effects, if any, the participants in the RECOVERY trial experienced, we do know how people reacted to similar treatments for respiratory illnesses. For example, corticosteroids like dexamethasone were used to treat patients with SARS who were critically ill in the hospital in 2003 and 2004, explains Dr. Jennifer Hanrahan, an infectious disease specialist and associate professor in the College of Medicine and Life Sciences at the University of Toledo. Among those patients, one-third ended up having serious long-term adverse effects, like osteoporosis. She says that the other concern with corticosteroids is that they can cause an increased risk of other infections. “For some of these patients who are critically ill — who are on ventilators — we are seeing some secondary bacterial infections when they’re in the hospital, so giving corticosteroids also potentially increases the risk of other infections,” she says.
Additionally, steroids may not be the best option for patients with conditions like diabetes or hypertension, says Dr. Christina Price, the chief of allergy and immunology at Yale School of Medicine. “And so then, when you put [patients] on steroids, their glucose increases significantly, and oftentimes they have to go on insulin or glucose control,” she tells Rolling Stone. Dela Cruz adds that patients without a prior diabetes diagnosis could also develop hyperglycemia.
Dela Cruz and Price are paying close attention to the results of the RECOVERY trial because they are co-authors of a separate peer-reviewed paper released today, looking at whether another anti-inflammatory drug (tocilizumab) could be an effective treatment for hospitalized COVID-19 patients. Unlike the RECOVERY trial, theirs was not a randomized control trial, and involved patients who were already being treated at Yale-affiliated hospitals. But their findings are promising: Patients treated with tocilizumab had a higher-than-expected survival rate with minimal side effects. And, according to Price, a majority of the participants in their study were people of color, and they found that with tocilizumab, black and Latinx patients had higher survival rates than white patients, when controlling for age. Though randomized trials are needed to confirm their findings, tocilizumab has the potential to be especially useful for people of color, who have been disproportionately impacted by coronavirus.
So is dexamethasone a miracle drug?
In short: not quite. Each of the medical professionals we spoke with stressed that these are only preliminary findings, and we still need more information on the drug before we know how it can actually be used in this pandemic. “It’s potentially exciting, at least from the information that is available, but I definitely think we have to be cautious,” Hanrahan says. She points out that so much of the data we’ve been getting on new COVID-related research have come from studies that haven’t yet been through the peer-review process. And sometimes, once the final version of the article is published, headlines on the research can change.
Even if further trials get the same results as the RECOVERY trial, keep in mind that dexamethasone is likely only effective in a handful of COVID-19 cases, in situations where a person has already been hospitalized. And according to Powell, there are still some key unanswered questions about dexamethasone. These include how the drug compares to other treatments that have been shown to be at least somewhat effective (like remdesevir and convalescent plasma) and which subset of patients are most likely to benefit, and least likely to have complications from steroid treatment.
Like most other aspects of this novel coronavirus, there are still many unknowns, so it will take more time and research before scientists are able to pinpoint the best possible treatments. “Compared to the other viral pneumonias and lung injuries that we’ve seen, [COVID-19] is a little bit different,” says Dela Cruz. “And in this case, I think, COVID-19 hasn’t been the most characteristic viral infection. So, this could be the answer, certainly, but we’ll have to wait for the full study and for other people to replicate it.”