Medical staff in a hospital ward for coronavirus patients in Wuhan, China, on Thursday.
Photo: str/Agence France-Presse/Getty ImagesTOKYO—Some doctors in China and Japan are using steroid drugs to treat coronavirus patients with difficult cases of pneumonia, generating a debate because the World Health Organization says they shouldn’t do so except in clinical trials.
Steroids in general tamp down inflammation, so they come to mind when doctors are trying to treat serious coronavirus-triggered pneumonia cases where the patient’s immune system goes into overdrive.
Inflammation can do more damage to virus-infected lungs in those cases than the virus itself, doctors say, and some believe a significant portion of the thousands of deaths from Covid-19, the disease caused by the new coronavirus, are related to this kind of reaction, essentially the body turning its fire on itself.
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“Mortality might be due to virally driven hyperinflammation,” wrote a group of U.K. doctors in the medical journal The Lancet on March 13, citing a study of patients in Wuhan, China, the initial center of the outbreak. “Therapeutic options include steroids” and other anti-inflammation measures, they said.
Cheng Zhenshun, head of respiratory and critical-care medicine at Zhongnan Hospital of Wuhan University, said doctors there applied that logic to treat patients “who had high fever, whose oxygen level suddenly dropped and who needed to be on a ventilator.” In those cases, “we started using steroids, for about four or five days, and we could pull back them back,” Dr. Cheng said in an interview.
But the WHO says there is no good evidence that the drugs work in such cases, citing studies that were done with other viral diseases including severe acute respiratory syndrome, or SARS, and Middle East respiratory syndrome or MERS.
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“Given the lack of effectiveness and possible harm, routine corticosteroids should be avoided unless they are indicated for another reason,” says the WHO’s official guidance for Covid-19 treatment, which accompanies its steroid section with a red “X” sign meaning “Don’t.”
Robert Fowler of the University of Toronto’s Sunnybrook Health Sciences Center, which is treating Covid-19 patients, said trials so far suggested steroids have been “a bit of a wash” in patients with life-threatening pneumonia caused by viral infections.
Dr. Fowler, whose research was cited in the WHO recommendation, said it was human nature to try something in desperate situations, but doctors’ observations outside of a clinical trial wouldn’t prove much.
“You’ll be overly influenced by one person in front of you,” he said. “Unless something has a penicillin effect”—a dramatic cure—“it’s really difficult to know whether what you’re seeing is chance.”
“ ‘Given the lack of effectiveness and possible harm, routine corticosteroids should be avoided…’ ”
“ ‘It is not right to say someone is wrong. In a sense, everyone is correct.’ ”
The debate played out in The Lancet recently as doctors at the University of Edinburgh in Scotland warned against steroid use. They cited research from the SARS epidemic in the early 2000s that showed side effects from steroid treatment including diabetes and a debilitating bone disease called avascular necrosis.
A Wall Street Journal investigation in 2003 found hundreds of Chinese patients suffered from side effects caused by aggressive and lengthy treatments with drugs including methylprednisolone, the steroid favored by Dr. Cheng in Wuhan and other Chinese doctors.
Dr. Cheng said he generally stopped or reduced the dose within four or five days to prevent side effects, whereas in the SARS cases clinicians said the steroid course routinely lasted more than a month.
In a letter to The Lancet, Chinese doctors criticized the Edinburgh team for relying on what they called inconclusive evidence and said prudent use of low to moderate steroid doses could help patients.
Trials of steroids in Covid-19 are getting under way, according to Dr. Fowler in Toronto, but for now doctors are relying on experience in a handful of cases.
Ciclesonide, a steroid also known by the brand name Alvesco and normally used for bronchial asthma treatment, was tried on three passengers from the cruise ship Diamond Princess who were diagnosed with the new coronavirus after the ship docked in Japan last month.
The three, treated in a hospital near Tokyo, needed oxygen support before receiving high doses of ciclesonide, according to Japanese-language case reports posted on the website of the Japanese Association for Infectious Diseases. One of the three, a 73-year-old woman, was barely able to eat or move, but two days after she got the drug she could breathe on her own and eat a meal, according to the report.
“We found this drug can suppress both viruses and inflammation,” said report co-author Tsuneo Morishima of Aichi Medical University. He said several other patients had been administered ciclesonide at hospitals in Japan. Doctors have reported the antiviral effect of ciclesonide in research that wasn’t peer-reviewed, but the reason is unknown.
Dr. Morishima said that because ciclesonide is inhaled directly into the lungs and hardly enters the bloodstream it was unlikely to cause the side effects seen in systemic use of steroids administered in the form of tablets or an injection. However, the drug has its own potential side effects, including mouth ulcers caused by drug residues in the mouth and possible stunted growth if taken long-term by children.
Japan’s health ministry has earmarked about $1 million for observational studies for ciclesonide. Earlier this month, it asked Teijin Pharma Ltd., a local licensee of the drug, to prepare the drug for trial use on coronavirus patients.
In these debates, “it is not right to say someone is wrong. In a sense, everyone is correct,” Dr. Morishima said. “It’s a matter of strategy about where to prioritize. Steroids are effective in suppressing inflammation…China prioritizes it.”
—Fanfan Wang in Beijing contributed to this article.
Write to Peter Landers at peter.landers@wsj.com and Miho Inada at miho.inada@wsj.com
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