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June 29, 2020

Promising Covid-19 drug could be 'harmful' to some patients, researchers say

Daily Briefing

    Earlier this month, researchers issued a press release announcing that a common, low-cost steroid called dexamethasone reduced the risk of death among patients with severe cases of Covid-19, though they didn't release the full study backing their claim until days later. Now that the full study has been published, scientists are finding that the drug may cause "more harm than good" in some patients, Roni Caryn Rabin reports for the New York Times.

    Researchers in press release say dexamethasone lowered risk of death in severe Covid-19 patients

    Scientists at the University of Oxford in a press release announced that a randomized controlled clinical trial showed that the low-cost steroid dexamethasone reduced the risk of death among patients with severe cases of Covid-19.

    At the time, the researchers said they had administered low doses of dexamethasone either orally or intravenously once per day to 2,104 patients with severe cases of Covid-19 at National Health Service (NHS) hospitals. According to the researchers, 4,300 hospitalized patients with severe cases of Covid-19 served as a control group and received standard care for the disease.

    The researchers said, when compared with the control group, dexamethasone decreased the number of deaths among patients on ventilators by one-third and reduced the number of deaths among patients being treated with supplemental oxygen by one-fifth. However, the researchers found that the steroid wasn't associated with any benefits among patients who were not receiving respiratory support.

    However, the researchers at the time did not release a full study detailing the trial's methods and results, which had not yet been peer reviewed. However, following the researchers' announcement, the World Health Organization said it would update its clinical guidance on how to treat patients with Covid-19 to reflect the findings and would "coordinate a meta-analysis to increase … overall understanding of this intervention." In addition, some American hospitals began using dexamethasone to treat Covid-19 patients.

    Dexamethasone could be 'risky' for some patients

    The researchers a few days later published their full study detailing the trial and results online—and some of the results were surprising to experts who weren't involved in the trial, Rabin reports.

    Primarily, while the study shows that dexamethasone can be beneficial for patients with severe Covid-19, the results also reveal that the treatment could be harmful for patients with mild cases of the disease, researchers who weren't involved in the trial have said.

    In addition, the results showed that patients with severe cases of Covid-19 who were not on respiratory support and were treated with the drug died at a slightly higher rate than similar patients who did not receive dexamethasone, though researchers said that difference was not statistically significant.

    Martin Landray, senior author of the study and a professor of medicine and epidemiology at Oxford, said it makes sense that the drug has different effects on patients who are in a different stage of the disease.

    "It's almost like a disease with two phases," according to Landray. "A phase where the virus dominates, and the immunological phase, where the damage the immune system causes is dominant."

    Stuart Neil, a professor of virology at King's College London, explained that dexamethasone most likely helps some patients with severe Covid-19 by "tamping down inflammatory responses in patients" experiencing what's known as "cytokine storm," which is an uncontrolled immune response that can be triggered by the new coronavirus and result in death. "It's almost certain [dexamethasone] is affecting the body's response against the virus, rather than inhibiting the virus itself," he said.

    But doctors are concerned that effect could hinder the body's protective immune response against the new coronavirus in patients with mild cases of Covid-19—which would "do more harm than good," Landry said.

    Landry explained that, [i]n the later phase" of Covid-19, "the immune system is [not] your friend—it's responsible for the lungs failing, and dampening it down with steroids helps the situation and improves the chance of survival." However, she said, "In the early phase of the illness, the immune system is your friend," as [i]t's fighting the virus, and dampening it is not a good idea."

    As such, Samuel Brown, an assistant professor of pulmonary and critical care medicine at the University of Utah School of Medicine who was not involved in the study, said, "It would likely be harmful to take dexamethasone as an outpatient treatment for Covid-19."

    In light of the new information, the study has left researchers with a lot of unanswered questions, and some are requesting that the scientists who conducted the study recreate their results in order to address outstanding unknowns regarding the long-term outcomes associated with the drug, as well as possible adverse outcomes, Rabin reports.

    In the meantime, Brown said patients with mild cases of Covid-19 "should not be trying to get people to prescribe them dexamethasone just in case" (Rabin, New York Times, 6/24).

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