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Infectious disease

Dexamethasone appears to help severe cases of COVID-19

The inexpensive, well-studied steroid could give doctors another tool in the coronavirus pandemic

by Lisa M. Jarvis
June 17, 2020 | APPEARED IN VOLUME 98, ISSUE 24

 

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An inexpensive, decades-old steroid appears to help some of the sickest COVID-19 patients survive, according to early results from a study conducted in hospitals in the UK. The data, which are only partially available and have not undergone peer review, suggest dexamethasone could treat the immune system overreaction that occurs in the most serious cases of the respiratory disease.

The UK study, dubbed RECOVERY (Randomised Evaluation of COVID-19 Therapy), has so far enrolled over 11,500 COVID-19 patients who were randomly given one of several treatments. Of those, 2,104 patients were given a low dose of dexamethasone, which is available as both a pill and IV treatment, for 10 days. The drug reduced deaths by one-third in people on ventilators and by one-fifth in people who needed oxygen compared with the 4,321 people in the trial who received standard care.

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Credit: Fotoarena/Newscom

To date, the only other drug to be clinically proven to have an effect on COVID-19 is Gilead Sciences’ remdesivir. The antiviral has been shown to reduce the length of hospital stays, but it has not been proven to lower the risk of death.

Infectious disease experts are excited that a cheap, long-used medicine could be useful in treating the novel coronavirus, which has already cost more than 440,000 lives.

But they remain circumspect about the limited dataset. “I’m intrigued by these results and would like to see all of the data; it certainly has the potential to alter the way patients are managed,” says Warner Greene, a virologist at the Gladstone Institute of Virology and Immunology. Like others interviewed by C&EN, Greene was unhappy about the way the results were released—with a press release rather than a full, peer-reviewed manuscript. But unlike many of the studies underway amid the pandemic, he notes, the trial has a robust design.

When our immune system is working properly, it finds a balance between “quick and effective inflammatory process that destroys or controls the virus and the negative feedback that stops the excessive inflammation, allowing our body to clear infected cells and repair damage tissues,” explains Gil Mor, an immunologist at Wayne State University.

The coronavirus infection becomes deadly when the immune response to the virus goes unchecked, and as Mor describes it, “inflammation brings more and more inflammation” in a feedback loop that overwhelms the body.

Dexamethasone works by broadly and powerfully suppressing that response. That it appears to do so safely and effectively surprised some. “I have a certain amount of caution because of the prior literature,” Greene says. Steroids have a checkered past in treating the serious immune overreactions that occur in other infections, including SARS (severe acute respiratory syndrome). One difference, he notes, is that in previous outbreaks, patients were given bursts of high doses of steroids, whereas this study offered low doses.

Drug companies are testing a range of newer medicines that dampen specific players in that immune response, an approach many had expected to be safer than steroids. Researchers point out that the RECOVERY trial is also testing one of those more precise immunomodulators—the IL-6 inhibitor tocilizumab.

“A somewhat cynical perspective is that there have been all of these studies looking at the top-of-the-line sewing machines . . . and here comes this, which is going back to using a needle and thread,” says Libby Hohmann, associate professor of medicine and infectious diseases at Massachusetts General Hospital.

Infectious disease experts tick off a number of questions they hope the final data will answer. For example, they wonder about the high death rate among all patients in the RECOVERY trial—up to 41% among those requiring ventilators and 13% among those requiring oxygen, “which seems quite astonishing,” Hohmann says.

H. Clifford Lane, clinical director at the National Institutes of Allergy and Infectious Diseases, who is overseeing COVID-19 studies at the NIH, isn’t necessarily concerned about the high death rate because some groups could be entering the study already at high risk.

The ability to compare populations “matters profoundly,” says Kathryn Radigan, a pulmonary and critical care physician at Chicago’s Cook County Health hospital. Radigan says she looks at each study that emerges to determine whether the patients who respond are similar the ones she is seeing in her own intensive care unit.

Doctors would also like a better handle on when in the course of the disease to give dexamethasone. For example, giving it too early, when the virus is revving up and the immune system needs to do its work to beat it back, could be counterproductive, Hohmann notes.

The study also raises questions about whether the steroid should be used with other treatments. “Should we be adding dexamethasone to remdesivir? Should we be reserving dexamethasone for people with certain inflammatory markers?” Hohmann asks. “These are really tough decisions.”

She adds that the NIH’s Adaptive Covid-19 Treatment Trial, which she is a part of, is considering how to combine therapies that work by different mechanisms, such as an antiviral and an anti-inflammatory drug.

And even if the data hold up when made available through a peer-reviewed publication, infectious disease experts caution that dexamethasone is not a miracle drug but just another tool. “We have one antiviral now, remdesivir, which has some degree of clinical efficacy in certain patient populations; it looks like now we may have another drug—an anti-inflammatory agent,” Lane says.

Still, most are encouraged by the idea that an inexpensive steroid could be another tool for doctors on the front lines of the COVID-19 pandemic. “The acid test is if I got sick and I was in the hospital, would I take dexamethasone?” Greene says. “And I think the answer is yes—but I’d sure like to read the paper first.”

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