Steroids May Reduce Death Rate Among Critically Ill COVID-19 Patients, Scientists Report

International clinical trials released Wednesday confirm hope that cheap and widely available steroids can help seriously ill patients survive COVID-19, the disease caused by the coronavirus.

Based on the new evidence, the World Health Organization issued a new treatment guide, strongly recommending steroids to treat critically ill patients, but not those with mild disease.

“Clearly, steroids are now the standard of care,” said Dr. Howard C. Bauchner, editor-in-chief of JAMA, who published five articles on the treatment.

The new studies include an analysis that gathered data from seven randomized clinical trials that evaluated 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 article and three related studies, along with an editorial describing the research as an “important step forward in treating COVID-19 patients.”

Corticosteroids should now be the first-line treatment for critically ill patients, the authors said. The only other drug that has been shown to be effective in seriously ill patients, and only modestly, is remdesivir.

Doctors often use steroids such as dexamethasone, hydrocortisone, and methylprednisolone to control the body’s immune system and relieve inflammation, swelling, and pain. Many COVID-19 patients die not from the virus but from the body’s overreaction to the infection.

In June, researchers from the University of Oxford found that dexamethasone improved survival rates in seriously ill patients. The researchers hoped that other inexpensive steroids could help these patients.

Evidence was lacking: After the Oxford researchers made their announcement, some clinical trials of steroids were stopped, as doctors hated to deny what appeared to be an effective treatment to study participants.

Steroids can have harmful side effects, especially in elderly patients, who make up the majority of very sick coronavirus patients. Medications can leave patients vulnerable to other infections, can raise blood glucose levels, and can cause confusion and delirium.

In 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. It is also necessary to identify the optimal doses and duration of treatment.

But overall, the scientists said, the new studies appeared to confirm the promise of this class of drugs for seriously ill patients with COVID-19.

The studies “are like the second hit of a double,” said Dr. Derek C. Angus, chairman of the department of intensive care medicine at the University of Pittsburgh, a co-author of one of the new studies and the analysis. .

“I had a big smile on my face when I saw the results,” added Angus. “This is a case of ‘one question asked, one question answered’, and that’s very rare.”

Analysis of the pooled data found that steroids were associated 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 conducted by a WHO task force that is striving to rapidly evaluate COVID-19 therapies.

Taken together, the new studies will bolster confidence in steroid use and address any lingering doubts on the part of some clinicians, said Dr. Todd Rice, associate professor of medicine and a physician of intensive care at the University of California School of Medicine. Vanderbilt.

In a new guideline, the WHO warned against indiscriminate use of steroids, emphasizing that patients who are not seriously ill are unlikely to benefit and may suffer from side effects. Unjustified use could deplete global supplies, depriving patients who really need the drugs.

The health organization began work on its guide in June, shortly after the University of Oxford published a preliminary report of its findings, partnering with researchers from seven clinical trials to conduct a meta-analysis and provide additional evidence in the fastest way possible. WHO officials. said.

They characterized the quality of the evidence in favor of steroid therapy for seriously ill patients as “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 that patients were alive and without mechanical ventilation.

Another study in France evaluated low doses of another steroid, hydrocortisone, in 148 patients. Those who received the drug were more likely to survive, but the results were not statistically significant because the trial was stopped early.

A third study evaluated different hydrocortisone regimens in 400 seriously ill COVID-19 patients in eight countries. It was also stopped prematurely, but the researchers concluded that there was a high probability that the treatment would improve outcomes.

When the Oxford results were announced in June, doctors around the world began using dexamethasone.

“I think there was some uncertainty as to whether the effect was real,” said Rice, co-author of an editorial accompanying the new articles in JAMA.

“This shows us that steroids are clearly beneficial in this population and clearly should be given, unless you can’t for some reason, which must be a pretty rare occasion.”

The drug remdesivir modestly shortens recovery time in critically ill COVID-19 patients, he noted, but it has not been shown to reduce deaths.

“People are dying from this disease and we want a treatment that we are confident will decrease mortality and save people’s lives,” Rice said.

Roni Caryn Rabin c.2020 The New York Times Company