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The Randomized Evaluation of COVID-19 Therapy Used Dexamethasone against COVID-19

Based on the findings and clinical trial tests that were conducted in the U.K., a common steroid drug treatment was miraculous as the dexamethasone cool down the severe symptoms that were being manifested by the COVID-19 patients. The medication is used to treat inflammatory diseases like rheumatoid arthritis.

The Randomized Evaluation of COVID-19 Therapy (RECOVERY) gathered 2,104 people hospitalized for the illness who were chosen to became the recipient to receive the common corticosteroid drug dexamethasone which is widely available in the pharmacies and drug stores. A control group of 4,321 patients received medical care in a standard way. 

“This is a major, breakthrough. I cannot overstate how important this is,” says Sam Parnia, an associate professor of medicine and director of critical care and resuscitation research at NYU Langone Health. He cautions that neither he nor his colleagues have seen a published manuscript, but notes, “this is coming from a very reputable group, with very large sample size.”

Scientific American spoke with Randy Cron, a professor of pediatrics and medicine at the University of Alabama at Birmingham, about the significance of the RECOVERY findings and why he’s optimistic about steroids as a treatment for patients hospitalized with the most severe coronavirus infections. Cron is an expert on cytokine storms, the out-of-control immune response that can occur in some illnesses, including COVID-19. Although the new results have not yet been published, he says he is confident that corticosteroids are a promising avenue for treatment for several reasons. “They’re likely to work, they’re cheap, and they’re available worldwide,” he says.

What do you make of the recently announced findings?

My overall take on this is that corticosteroids are likely to be the way to help the planet. Other drugs are expensive and not available worldwide. I wasn’t surprised when I saw the announcement. There was another report out there—not a randomized trial, but a historical cohort control study out of Michigan [the May Clinical Infectious Diseases study]. It also suggested [corticosteroids] could benefit COVID-19 patients. We used steroids for variety of cytokine storm syndromes long before COVID-19 came along. It makes sense that they would work [for COVID-19]. There have been a lot of case series [studies] of [other immunomodulators such as inhibitors of interleukin-1] (IL-1) and interleukin-6 (IL-6), which are also saving [the lives of people with COVID-19]. The big take-home message isn’t so much that steroids work but that the virus is [just] the trigger. And really what’s killing people is the immune response to the infection.

Weren’t some scientists hesitant to use corticosteroids to treat COVID-19 because of the risk of weakening the body’s response to the virus?

The [World Health Organization] and a lot of other groups [have, until now, been] opposed to using steroids for COVID-19. A lot of that was based on [studies of] SARS and MERS (other deadly coronaviruses), [but] the data are kind of mixed—a lot of them are not great data. Some important things to note: The timing of [when the drug is given] is important. So is the population treated—this is not something you should be giving to asymptomatic people, to people who are [well] enough to ride it out at home with a flulike illness or anywhere in between. The [ideal] patients are the ones who are sick enough to need hospitalization for respiratory distress from COVID-19. And you should treat them before the point that they need to be invasively mechanically ventilated or otherwise require intensive care. In terms of timing, the first five to seven days of symptoms are probably not when you want to treat the patient. When the patient is in respiratory distress requiring hospitalization—that’s the point when you want to dampen the immune system. Likely the dosing is [also] important. You probably don’t need to use the high doses used [to treat] cytokine storms [in other diseases]. Moderate doses may suffice.

Dexamethasone and other steroids are broad-brush treatments that suppress the immune system as a whole. How do these compare with drugs that are targeted to specific immune system molecules, which are also being tested against COVID-19?

This is a worldwide pandemic, and we’re not immune to it. In this country, [roughly] two million people [have been] infected. My guess is it’s more like 20 million if we tested everyone. If [up to 20 percent of them] need to be hospitalized, you are not going to have enough targeted [cytokine-blocking drug] therapies available. We will have enough corticosteroids. The downside is there are more side effects. If you have those more targeted drugs available, sure, you should use them. But if you’re in a country where you don’t have them, corticosteroid drugs could be a more feasible option.

What about side effects?

These drugs definitely will have side effects. Steroids are problematic; there’s no doubt about that. But if the choice is [potential side effects versus] death, side effects may be a relatively small price to pay.

Studies of steroid treatment for SARS and MERS infections found little or no benefit. Why should it work for COVID-19?

Some studies showed [steroids] helped. Some [found] they do more harm than good. Some were randomized [studies]; some were not. Some were controlled; some were not. Now we are so inundated with data—this is way bigger than SARS or MERS in terms of the numbers [of individuals] infected.

I’ve talked to people all over the world. A colleague at Temple University in Philadelphia reports their center has treated more than 1,500 individuals [some of whom were] not in a clinical trial. Everyone admitted [to the university’s hospital] gets a moderate dose of corticosteroids. Many patients were from the inner city and had a lot of comorbid conditions. Approximately 50 percent were African American; 30 percent were Hispanic—[all groups that are disproportionately at risk of severe COVID-19 infections]. Their mortality rate was under 7 or 8 percent. I’m pretty convinced [that corticosteroids are effective for severe cases of COVID-19 pneumonia].

The U.K. is now making dexamethasone a standard of care for patients hospitalized with severe COVID-19. Do you think this decision is justified?

It’s likely a better standard of care than [the antiviral drug] remdesivir. We’ll see if that’s the right decision. Even the kids who are getting [an inflammatory syndrome post-COVID-19 infection]—they do well on steroids.

The [biggest] concern I have with steroids is that people are going to want to start taking them at home—that’s not a good thing. This is really for hospitalized patients under the care of a clinician.

We’ve seen other drugs being touted as treatments for COVID-19 before. Why should this one be different?

 [Most of those treatments] were being driven by infectious disease doctors, not doctors who treat cytokine storms. [Many of the drugs were] antivirals. There is going to be more steroid data coming out, but it’s going to lag [behind that on] antivirals.

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