Dexamethasone may or may not be a breakthrough coronavirus treatment

The corticosteroid shows promise in major – though yet-unpublished – British clinical trial; drug has been given to UCHealth COVID-19 patients since March.
June 19th, 2020
Covid-unit nurse getting something out of a drawer. nurses are now giving dexamethasone to some coronavirus patients.
A British study’s preliminary results indicate that an old, inexpensive corticosteroid (Dexamethasone) may do more to save acute coronavirus patients than anything medical science has found so far. Will it be a major breakthrough? Photo by Joel Blocker, for UCHealth.

When an old drug made big news on June 16, it came to no surprise to a young UCHealth physician.

The drug was dexamethasone. It was first approved in October 1958 when Dwight Eisenhower was president, NASA was born, and Pan Am flew the first commercial flight across the Atlantic.

The news this month was a major British study’s preliminary findings that seriously ill COVID-19 patients who received dexamethasone, a corticosteroid, had a 35% better survival rate than patients who did not receive the drug. In the face of growing doubts about the effectiveness of hydroxychloroquine against the disease, the apparently modest improvement of patients who receive the antiviral remdesivir, and the lack of other proven coronavirus therapies, the British study’s preliminary findings were a rare ray of light amid a therapeutic outlook stuck in a predawn gray.

The young physician is Dr. Josh Douin, and he wasn’t surprised because he and other intensive-care physicians at UCHealth University of Colorado Hospital on the Anschutz Medical Campus have been giving intravenous dexamethasone to seriously ill coronavirus patients since the dawn of the Colorado outbreak three months ago. Douin, a University of Colorado School of Medicine anesthesiologist and critical-care medicine specialist, has in fact proposed, with virologist Dr. Thomas Campbell and Emergency Medicine physician Dr. Adit Ginde, a clinical trial to quantify the safety and effectiveness of dexamethasone on COVID-19 patients.

Calming the storm

Douin joined many in the medical community in advising caution with respect to the British study’s initial report, which came in the form of a press release. It could well be, for example, that the patients who received dexamethasone weren’t as sick as those who didn’t, or that the study had other potential flaws, he says.

A photo of Dr. David Josh Douin, who talks about dexamethasone as a coronavirus treatment
Dr. David Josh Douin, who discusses if dexamethasone is a breakthrough coronavirus treatment.

“Distributing via press release is no substitute for a peer-reviewed article,” he said.

That said, Douin and others recognize dexamethasone’s long-recognized ability to settle down the immune system, and that the drug’s immunosuppressive effect might quell the hyperinflammation caused by the body’s immune response to the coronavirus. The medical community increasingly recognizes cytokine storm-triggered autoimmunological assaults as the primary culprits in the most serious coronavirus cases. Those inflammatory attacks can target not only the lungs, but also the heart, brain, gastrointestinal tract, kidneys, and blood.

The British team is well-respected, and the study design as well as the large number of participants bolster hopes that the findings will hold up. The team’s chief investigators say they went public prior to peer-reviewed publication because the patients who got dexamethasone did so much better than those not receiving the drug – to the point that the investigators halted the trial on June 8 and got the word out as quickly as they could.

The study involved 2,104 patients who received 6 milligrams of intravenous dexamethasone once a day for 10 days. When the team compared outcomes at 28 days with those of 4,321 patients who received usual care, the researchers found deaths among patients on ventilators to be 35% lower and deaths among patients requiring oxygen only to be 20% lower than the control group. Patients who didn’t require respiratory support fared no better or worse on the drug, the team found.

Douin describe the results as “very promising,” all the more so because dexamethasone is widely available, widely used, and cheap: the medical course the British study used would cost about $50, he said.

Hope @ UCHealth

While dexamethasone hasn’t yet been formally studied with coronavirus patients at UCHealth University of Colorado Hospital, many patients have received it, Douin says. The impetus was a Spanish-led study published in February that showed marked improvement among patients with acute respiratory distress syndrome (ARDS). That disease has many triggers, COVID-19 among them. Douin described a 34-year-old patient who, given a 20-milligram dose of dexamethasone on each of the first five days and 10-milligram doses on days six through 10 (the treatment regimen outlined in the Spanish study) turned around quickly. Douin cautions that, while dexamethasone seems also to have benefitted a handful of other patients, some of the UCHealth ICU patients who received the corticosteroid later died, too.

“I suspect it’s helping, but my suspicions are not gold-standard evidence, and they’re not a clinical trial,” Douin said.

The British dexamethasone announcement came as researchers around the world study whether existing drugs known to tamp down unwanted immune responses may shelter COVID-19 patients from cytokine storms. Some are broad-based anti-inflammatories; some target particular cytokines such as interleukin-6 and interleukin-1. One of those drugs, the IL-1 receptor antagonist anakinra, was developed based on pathbreaking research by the late University of Colorado School of Medicine immunologist William Arend.

Given that dexamethasone has been on the job for 62 years, it’s well understood, Douin says. It’s given to the vast majority of UCHealth surgery patients as a nausea suppressant, and it’s used to treat edema and swelling and also as a pain-reducer for cancer patients, he says. That dexamethasone is also a mainstay for patients after cataract eye surgery hints at the drug’s versatility.

The drug can have serious side-effects also, though, Douin says: it can increase blood sugar to the point that insulin is required, and it can cause muscle weakness and neuropathy. As advertised, dexamethasone also suppresses the immune system, which can slow wound healing and hinder the body’s ability to fight infection.

That last side effect of corticosteroids, Douin says, led to initial caution with respect to dexamethasone and its brethren as COVID-19 treatments. Patients with viral pneumonia caused by SARS and MERS coronaviruses had a harder time clearing the virus when on corticosteroids and fared no better than patients without the corticosteroids.

As Douin and physicians around the world await the British team’s peer-reviewed report (he expects it may be published in the next four to six weeks), UCHealth will continue to treat its most serious patients as it has been doing – including with dexamethasone.

Douin is hoping the study lives up to the press release.

“I think this is a new tool that gives us hope, and it’s one more thing we can use for the sickest patients with COVID-19,” he said.

 

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About the author

Since 2008, Todd Neff has written hundreds of stories for University of Colorado Hospital and UCHealth. He covered science and the environment for the Daily Camera in Boulder, Colorado, and has taught narrative nonfiction at the University of Colorado. He was a 2007-2008 Ted Scripps Fellowship recipient in Environmental Journalism at CU.

His latest book, "The Laser That’s Changing the World," tells the story of the inventors and innovators who saw, and ultimately realized, the potential of lidar to help solve problems ranging from smokestack-pollution detection, ice-sheet mapping, disaster recovery, and, ultimately, autonomous-vehicle guidance, among many other uses. His first book, "From Jars to the Stars," recounts how Ball Aerospace evolved from an Indiana jar company - and a group of students in a University of Colorado basement - to an organization that managed to blast a sizable crater in the comet 9P/Tempel 1. "Jars" won the Colorado Book Award for History in 2012.

Todd graduated with a business degree from the University of Michigan, where he played soccer, and with a master’s degree from the Fletcher School of Law and Diplomacy at Tufts University. Before becoming a journalist at the turn of the millennium, he was an IT and strategy consultant. He once spoke fluent Japanese and still speaks fluent German.

When not writing, he spends time with teenage daughters and wife Carol, plays soccer, and allows himself to be bullied by a puggle he outweighs by a factor of seven.