International clinical trials published on Wednesday confirm the hope that cheap, widely available steroid drugs can help seriously ill patients survive Covid-19, the illness caused by the coronavirus.
Based on the new evidence, the World Health Organization issued new treatment guidance, strongly recommending steroids to treat severely and critically ill patients, but not to those with mild disease.
“Clearly, now steroids are the standard of care,” said Dr. Howard C. Bauchner, the editor-in-chief of JAMA, which published five papers about the treatment.
The new studies include an analysis that pooled data from seven randomized clinical trials evaluating three steroids in more than 1,700 patients. The study concluded that each of the three drugs reduced the risk of death.
JAMA published that paper and three related studies, along with an editorial describing the research as an “important step forward in the treatment of patients with Covid-19.”
Corticosteroids should now be the first-line treatment for critically ill patients, the authors said. The only other drug shown to be effective in seriously ill patients, and only modestly at that, is remdesivir.
Steroids like dexamethasone, hydrocortisone and methylprednisolone are often used by doctors to tamp down the body’s immune system, alleviating inflammation, swelling and pain. Many Covid-19 patients die not of the virus, but of the body’s overreaction to the infection.
In June, researchers at Oxford University discovered that dexamethasone improved survival rates in severely ill patients. Researchers had hoped that other inexpensive steroids might help these patients.
The evidence had been lacking: After the Oxford researchers made their announcement, some clinical trials of steroids were halted, as doctors were loathe to withhold what appeared to be an effective treatment from study participants.
Steroids can have harmful side effects, especially in elderly patients, who make up the majority of very ill coronavirus patients. The drugs may leave patients vulnerable to other infections, may raise blood glucose levels, and may cause confusion and delirium.
In the clinical trials, only the sickest patients were treated with steroids, and it is not certain that those who are less ill will benefit or be harmed. The optimal doses and duration of treatment also need to be identified.
But over all, the scientists said, the new studies appeared to confirm the promise of this class of drugs for patients severely ill with Covid-19.
The studies “are like the second punch of a one-two punch,” said Dr. Derek C. Angus, chair of the department of critical care medicine at the University of Pittsburgh, who co-authored one of the new studies and the analysis.
“I had a big smile on my face when I saw the results,” Dr. Angus added. “This is a case of, ‘A question asked, a question answered,’ and that’s so rare.”
The analysis of pooled data found that steroids were linked with a one-third reduction in deaths among critically ill Covid-19 patients. Dexamethasone produced a 36 percent drop in deaths in 1,282 patients treated in three separate trials.
Hydrocortisone, tested in 374 patients in three trials, appeared to reduce deaths by 31 percent, and a small trial of methylprednisolone in 47 patients resulted in a 9 percent drop in deaths. The analysis was carried out by a W.H.O. working group that is making efforts to rapidly evaluate Covid-19 therapies.
Taken together, the new studies will bolster confidence in the use of steroids and address any lingering hesitancy on the part of some physicians, said Dr. Todd Rice, an associate professor of medicine and critical care physician at Vanderbilt University School of Medicine.
Frequently Asked Questions
Updated September 1, 2020
Why is it safer to spend time together outside?
- Outdoor gatherings lower risk because wind disperses viral droplets, and sunlight can kill some of the virus. Open spaces prevent the virus from building up in concentrated amounts and being inhaled, which can happen when infected people exhale in a confined space for long stretches of time, said Dr. Julian W. Tang, a virologist at the University of Leicester.
What are the symptoms of coronavirus?
- In the beginning, the coronavirus seemed like it was primarily a respiratory illness — many patients had fever and chills, were weak and tired, and coughed a lot, though some people don’t show many symptoms at all. Those who seemed sickest had pneumonia or acute respiratory distress syndrome and received supplemental oxygen. By now, doctors have identified many more symptoms and syndromes. In April, the C.D.C. added to the list of early signs sore throat, fever, chills and muscle aches. Gastrointestinal upset, such as diarrhea and nausea, has also been observed. Another telltale sign of infection may be a sudden, profound diminution of one’s sense of smell and taste. Teenagers and young adults in some cases have developed painful red and purple lesions on their fingers and toes — nicknamed “Covid toe” — but few other serious symptoms.
Why does standing six feet away from others help?
- The coronavirus spreads primarily through droplets from your mouth and nose, especially when you cough or sneeze. The C.D.C., one of the organizations using that measure, bases its recommendation of six feet on the idea that most large droplets that people expel when they cough or sneeze will fall to the ground within six feet. But six feet has never been a magic number that guarantees complete protection. Sneezes, for instance, can launch droplets a lot farther than six feet, according to a recent study. It’s a rule of thumb: You should be safest standing six feet apart outside, especially when it’s windy. But keep a mask on at all times, even when you think you’re far enough apart.
I have antibodies. Am I now immune?
- As of right now, that seems likely, for at least several months. There have been frightening accounts of people suffering what seems to be a second bout of Covid-19. But experts say these patients may have a drawn-out course of infection, with the virus taking a slow toll weeks to months after initial exposure. People infected with the coronavirus typically produce immune molecules called antibodies, which are protective proteins made in response to an infection. These antibodies may last in the body only two to three months, which may seem worrisome, but that’s perfectly normal after an acute infection subsides, said Dr. Michael Mina, an immunologist at Harvard University. It may be possible to get the coronavirus again, but it’s highly unlikely that it would be possible in a short window of time from initial infection or make people sicker the second time.
In new guidance, the W.H.O. warned against indiscriminate use of steroids, emphasizing that patients who are not severely ill are unlikely to benefit and may suffer side effects. Unwarranted use could deplete global supplies, depriving patients who genuinely need the medications.
The health organization started work on its guidance in June, shortly after Oxford University published a preliminary report of its findings, partnering with investigators of seven clinical trials in order to conduct a meta-analysis and provide additional evidence in the most expeditious manner, W.H.O. officials said.
They characterized the quality of the evidence in favor of steroid treatment for severely ill patients as one of “moderate certainty.”
Among the other studies published Wednesday was a Brazilian trial of 299 patients with acute respiratory distress syndrome that compared dexamethasone treatment with regular care. The steroid significantly improved outcomes, increasing the number of days patients were alive and free of mechanical ventilation.
Another study in France evaluated low doses of another steroid, hydrocortisone, in 148 patients. Those receiving the drug were more likely to survive, but the results were not statistically significant because the trial was stopped early.
A third study tested varying hydrocortisone regimens in 400 seriously ill Covid-19 patients in eight countries. It was also stopped prematurely, but the researchers concluded there was a strong probability that the treatment improved outcomes.
When the Oxford results were announced in June, physicians worldwide started using dexamethasone. “I think there was some uncertainty about whether the effect was real,” said Dr. Rice, who co-authored an editorial accompanying the new papers in JAMA.
“This shows us steroids are clearly beneficial in this population and should clearly be given, unless you absolutely can’t for some reason, which needs to be a pretty rare occasion.”
The drug remdesivir modestly shortens time to recovery in critically ill Covid-19 patients, he noted, but has not been shown to reduce fatalities. “People are dying from this disease, and we want treatment that we are confident will decrease mortality and save people’s lives,” Dr. Rice said.