The research was published in the Journal of the American Medical Association (JAMA) on September 2. In addition to the WHO meta-analysis, three clinical trials of steroids were also published in JAMA.
The patients with severe COVID-19 who received one of three corticosteroids—dexamethasone, hydrocortisone, or methylprednisolone—had an estimated 20% reduced risk of dying from the infection.
About 60% of patients with severe COVID-19 survive without taking steroids. The research showed that the survival rate went up to 68% for patients who were treated with the medication.
The mortality results were consistent across the seven trials, with dexamethasone and hydrocortisone showing similar results. However, the researchers could not tell if the effects of methylprednisolone were similar because there were not enough patients enrolled in those trials.
The Corticosteroid Connection
Corticosteroids have been assessed in the past for patients with pneumonia, septic shock, and acute respiratory distress syndrome (ARDS). Many COVID-19 patients develop ARDS—a potentially fatal condition that occurs when a patient’s immune system attacks the lungs. Corticosteroids do not target SARS-CoV-2 (the virus that causes COVID-19), but they do help prevent ARDS.
Cortisol and synthetic corticosteroids—including dexamethasone, hydrocortisone, and methylprednisolone—regulate the immune system (particularly inflammatory responses) as well as regulate glucose metabolism, Nancy R. Gough, PhD, an adjunct associate professor at George Washington University, tells Verywell.
Severe COVID-19 appears to be caused by an exacerbated inflammatory response. Corticosteroids can be used to turn down the body’s out-of-control response to inflammation, Gough says.
“Corticosteroids are largely anti-inflammatory drugs,” Todd W. Rice, MD, an associate professor of medicine at Vanderbilt University Medical Center, tells Verywell.
“We think they work by decreasing inflammation that the body develops from the SARS-CoV2 virus,” Rice says.
The inflammation often causes additional damage to the lung and other organs. By reducing the inflammation with corticosteroids, it can improve outcomes for patients with more severe COVID-19.
However, corticosteroids do not promise an immediate response, Rice says. “Patients are not suddenly better when corticosteroids are given. The disease process is still quite protracted, even when corticosteroids are given. But the inflammatory markers improve, which is one of the ways doctors can monitor if the corticosteroids are working.”
Dexamethasone: A New Standard in COVID-19 Care
Other studies have also explored the use of steroids to treat patients with COVID-19. Some of the data cited by the WHO comes from the RECOVERY trial.
A July report of preliminary data on the trial was published in the New England Journal of Medicine. For the trial, 6,425 patients were randomized into two groups: 2,104 received dexamethasone and 4,321 did not.
The randomized patients on ventilators or oxygen who were given dexamethasone had lower monthly mortality compared to patients who did not receive respiratory support.
The WHO’s meta-analysis that appeared in JAMA in September included RECOVERY trial data. The data showed that 222 of the 678 patients who were randomly given the medicine died. Of the 1,025 patients who did not receive the medication, 425 died.
Hallie Prescott, MD, a professor at the University of Michigan, along with Rice, penned an accompanying JAMA editorial about the meta-analysis. Both authors said that the studies provided definitive evidence that corticosteroids should be the primary treatment for patients who are critically ill with COVID-19.
The WHO recently released new treatment guidelines endorsing corticosteroids as the standard of care for patients with “severe and critical” COVID-19. The WHO said patients should be on the medication for seven to 10 days.
Overall, there is strong evidence from randomized clinical trials and a meta-analysis in support of treating some COVID-19 patients with dexamethasone. Gough says the WHO made a scientifically informed decision based on strong evidence.
“This is the only treatment that has shown a clear and convincing reduction in mortality,” Gough says.
“I think the data are pretty definitive now. We now have multiple large randomized controlled studies that show [the] benefit of corticosteroids for patients with severe COVID," Rice says. “The WHO took all of the data into consideration, and the data overwhelmingly support the use of corticosteroids and demonstrate that they improve outcomes in patients with severe COVID-19.”
Rice adds corticosteroids also decrease the need for ventilation and help patients come off ventilation faster.
Rice explains that the research shows that corticosteroids are better than remdesivir, an antiviral medication, for treating COVID-19. Preliminary data published in May in the New England Journal of Medicine showed faster recovery times. However, the results were only found in patients who received oxygen therapy—they did not extend to people with mild cases or patients on ventilators.
The assessment of possible COVID-19 treatments is ongoing, and it’s possible that other options may help patients or add benefits to corticosteroid use.
“But currently, corticosteroids are the best treatment we have for patients with COVID-19,” says Rice.
Corticosteroids Aren’t Right for All COVID Cases
Experts say that patients who do not have critical cases of COVID-19 are not ideal candidates for taking corticosteroids.
“Indiscriminate use of any therapy for COVID-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially life-saving therapy,” the WHO said in a statement.
Perhaps even more important than conserving supplies is the danger of taking corticosteroids if you don’t have severe COVID-19.
“It is important for people to realize that taking corticosteroids too soon in the course of any infection impairs the body’s ability to fight the infection,” Gough says. “So, people should not consider corticosteroids as medicine that should be used for COVID-19 with mild symptoms or just for someone who has a positive COVID test result.”
Corticosteroids aren’t right for every patient—even in those with critical cases. For example, they can cause hyperglycemia, which means people who have diabetes and severe COVID-19 need to have their blood sugar closely monitored.
“These medications are not preventative and are detrimental if taken too soon,” Gough says.
Gough adds that they must be carefully administered, and the dose should be slowly reduced over time. This allows the adrenal glands to resume the production of cortisol, and proper blood sugar regulation to be restored.
Some patients with comorbidities such as pulmonary disease or heart disease would have difficulty recovering and surviving any serious respiratory infection that affected the lungs whether or not they were given corticosteroid treatment, says Gough.
Corticosteroids are often used in any patient receiving ventilation support for ARDS, and elderly patients with comorbidities are still those at most risk of dying, Gough says. “Corticosteroids will not save all patients with severe COVID-19, but are likely to have the most benefit for those who would have normally survived other serious respiratory infections."
Rice agrees.
“People shouldn’t think that corticosteroids save everybody,” Rice says. “While they do reduce deaths and improve survival, patients are still dying from COVID-19, even when they are treated with corticosteroids.”
Rice emphasizes that the findings are not “a free pass” to relax and stop taking steps to prevent the spread of COVID-19. “The virus still causes lots of issues, and data are starting to emerge that suggest that it may cause longer-term issues with fatigue and memory and thinking, also,” he says.
The medical community needs to conduct and complete more trials for other COVID-19 treatments, says Jonathan A. C. Sterne, PhD, a medical statistics and epidemiology professor at the University of Bristol in England. Sterne worked with the WHO on the meta-analysis.
Sterne hopes the public understands that corticosteroids are not a cure for severe COVID-19. It remains a deadly disease, especially for older people and those with underlying health conditions. “We urgently need high-quality research…definitive randomized trials…for both treatments and vaccines," he says.
The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.
