The search for treatments for COVID-19 has most recently led to a medication already known to help patients in severe lung failure known as acute respiratory distress syndrome, or ARDS. The drug, dexamethasone, is a corticosteroid that is used to treat a variety of conditions, not just ARDS, as an anti-inflammatory and immunosuppressant agent.
“It is used in a number of diseases — autoimmune diseases, inflammatory diseases — and can be use topically, intravenously, orally, in multiple formulations,” says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who is the leading national expert in the fight against COVID-19. “It is very, very well known and universally used for inflammation.” Dexamethasone is routinely used when patients are on ventilators for ARDS, Fauci says.
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Dexamethasone and COVID-19
Would dexamethasone help patients suffering from ARDS because of SARS-CoV-2, the novel coronavirus that causes the disease? A study out of the U.K. known as the RECOVERY Trial offers a qualified but promising yes. Researchers tested dexamethasone on patients hospitalized because of COVID-19 and found it to have significant benefits for critically ill patients. According to preliminary findings that have yet to be peer reviewed, the treatment reduced deaths by about one-third for patients on ventilators and by about one-fifth for patients requiring supplemental oxygen.
Though encouraging, the study does have some drawbacks. “It wasn’t a perfect study by any means. There is understandable and appropriate concern when looking at prepublication data,” Fauci admits. Dr. Michael A. Matthay, professor of medicine and anesthesia and associate director of critical care medicine at University of California–San Francisco, adds that while there is a long history of steroid use in ARDS, results of other studies on its efficacy have been “very mixed, with no consistent results.”
In fact, studies on patients with viral pneumonia suggest steroids could cause harm by reducing the lungs’ ability to clear that virus, Matthay says. The RECOVERY Trial on how effective dexamethasone is for coronavirus patients, he says, “was a complicated trial, and most of us in the field feel it’s important to see the final, published, peer-reviewed manuscript before reaching a final decision.”
The National Institutes of Health’s COVID-19 Treatment Guidelines panel was given a presentation by the RECOVERY investigators, Fauci says, and, despite the study’s problems and the fact that, as the panel states, other studies on steroid use in COVID-19 patients “have yielded conflicting results; both beneficial and harmful,” decided to add dexamethasone to its list of treatments for patients requiring ventilation or supplemental oxygen. “They were impressed with the data, and thought it was strong enough to make a recommendation to use this,” Fauci says.
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‘The Worse You Are, the More Positive Effect’
It makes theoretical sense, at least, that a corticosteroid would help treat severe respiratory disease caused by SARS-CoV-2. In these extreme cases, the virus itself is not the main problem. Instead, the infection appears to promote the expression and release of proteins called pro-inflammatory cytokines. In effect, the body’s immune system seems to kick into overdrive as it responds to the infection, with potentially harmful results. “In severe cases, these cytokines can lead to tissue damage, most significantly lung damage, and cause other types of organ dysfunction,” says Dr. Karen Ravin, chief of infectious diseases, Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware.
A corticosteroid medication like dexamethasone suppresses this over-vigilant inflammatory response, Ravin says: “It does not act directly on the virus but rather can modulate the body’s response to infection.” Curbing inflammation seems to be critical in preventing death, and that makes dexamethasone a potential life-saver.
However, “because corticosteroids suppress the immune system’s response to an infection, there is concern that using them at the wrong time might interfere with the body’s ability to fight off the virus,” Ravin warns. That’s why the NIH guidelines panel does not recommend its use on patients who are not on ventilators or supplemental oxygen. And that makes perfect sense to Fauci. “That fits in exactly with the pathogenesis (of the virus),” he says. “Early in the disease you want to block the virus. You don’t want to suppress the immune system, you want the immune system to work. The worse you are, the more positive effect dexamethasone has.”
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Further Study Is Needed
Everyone agrees that this is not the final word on dexamethasone. “Further study is needed to see if these results can be reproduced in other centers and to determine the optimal dose, timing and patient population in which dexamethasone should be used,” Ravin says.
“We know in ARDS critical care that a second confirmatory trial is really important,” Matthay agrees. “One way to resolve this, if the results are not clear cut, is to do another trial.”
Fauci doesn’t argue with that, but says that the RECOVERY Trial “has proven what many people have been doing anyway. We all agree it’s not a perfect study, but the data are solid enough in the eyes of a considerable number of expert people to make a recommendation to use this drug in advanced lung disease.”
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How Does Dexamethasone Help COVID-19 Patients With Severe Lung Disease? originally appeared on usnews.com
