By Peter Fimrite, San Francisco Chronicle, June 17 2020
A steroid long used in hospitals to control inflammation significantly reduced fatalities in seriously ill COVID-19 patients during a drug trial, marking the first time any coronavirus treatment has proven to prevent deaths, said a University of Oxford study released Tuesday.
The drug dexamethasone reduced deaths among patients on ventilators by one-third and cut fatalities for people receiving oxygen by one-fifth in a drug trial involving 6,425 coronavirus patients in the United Kingdom, university scientists said.
“Dexamethasone is the first drug to be shown to improve survival in COVID-19,” said Peter Horby, an infectious disease expert at the University of Oxford, in a statement. “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients.”
Most medical professionals in the Bay Area said the results are encouraging, but they cautioned people not to get too excited and make a run on stores looking for the drug, especially given that it appears to work only on severely ill patients.
Lee Riley, an infectious disease expert at UC Berkeley, said the study must be reviewed by other experts and more, larger trials will be necessary before it becomes standard treatment in the United States.
“If this is reproduced by other studies, that would make it a very encouraging, relatively inexpensive way to decrease deaths from this disease,” Riley said.
Bay Area infectious disease experts said the low-cost steroid is often used in intensive care units for other ailments to control inflammation. It had mixed results, however, when it was tested on the SARS coronavirus detected in China in 2002, showing modest improvement in some trials and potentially ill effects in others.
Inflammation, though, is a serious problem among COVID-19 patients whose immune systems sometimes overreact to the disease, worsening infections in the lungs and other organs.
The researchers, including doctors, nurses and pharmacists at more than 175 hospitals in the U.K., gave 6 milligrams a day of dexamethasone to 2,104 patients for 10 days while the rest of the people in the trial were treated for the disease in the normal way. They then compared the two groups and found that ventilated patients, who have the highest death rate, benefited the most.
The study said the steroid eased the intense inflammatory response, known as a cytokine storm, that happens in some patients. That’s a particular problem in those who develop acute respiratory distress syndrome, which is characterized by fluid in the lungs, according to scientists at Stanford and UCSF.
The trial results have not yet been published in a peer-reviewed journal, and medical experts in the Bay Area and across the United States plan to study the drug further to confirm the results. The trials showed the drug was ineffective in treating patients who did not need respiratory intervention.
Some Bay Area doctors urged caution, especially considering how other promising treatments have been rushed into use only to be retracted or walked back in recent months.
For example, the Food and Drug Administration on Monday withdrew emergency use authorizations for hydroxychloroquine and chloroquine, both of which were touted by President Trump despite concerns about their safety and effectiveness. Doctors have said hydroxychloroquine can cause heart problems. Clinical trials show the two drugs “are unlikely to produce an antiviral effect,” FDA chief scientist Denise Hinton said in a letter announcing the decision.
Warner Greene, a senior virologist and director at San Francisco’s Gladstone Center for HIV Cure Research, said steroids have all kinds of side effects, including making patients more prone to infection and worsening the effects of diabetes. Long-term users can also develop osteoporosis and other disabling bone, tendon and muscular problems.
That, however, is a small price to pay to save a life.
“There’s just a whole series of effects, but when you have SARS-CoV-2 and you are dying of ARDS, these are small effects,” Green said, pointing out that the dosages used in the study were small and that the drug was administered for a short period of time. “So I think it’s encouraging. This is good news.”
Dr. Melanie Ott, a virologist and senior investigator with Gladstone and a professor at UCSF, said doctors know steroids can be helpful with inflammation, but the dose has to be monitored carefully or it could cause harm.
“These new studies show benefit in patients with severe disease and only with a relatively low dose of steroids, which is important,” Ott said. “The drug suppresses inflammation and likely helps to keep the cytokine storm in the lung at bay to reduce severe outcome. It is important to know for which patients it has a benefit and at what dose, so treatment recommendations can be uniform.”
Annie Luetkemeyer, an infectious disease specialist at UCSF, said the drug would be convenient because it is already widely available in the United States, but it may not be such a big deal in the Bay Area, where the death rate is low — it’s less than 5% at Zuckerberg San Francisco General Hospital.
“We need to be thoughtful about risks and benefits of steroids,” Luetkemeyer said. “However, I’m thrilled to see any intervention with a mortality benefit, particularly in critically ill patients.”
The promising results prompted the British government to make dexamethasone widely available in the United Kingdom for use on COVID-19 patients.
“Dexamethasone reduces the risk of death among patients with severe respiratory complications,” said Martin Landray, a professor of medicine and epidemiology at Oxford and one of the chief investigators. “It is fantastic that the first treatment demonstrated to reduce mortality is one that is instantly available and affordable worldwide.”