Ended soon
Researchers in England say they have the first evidence that a drug
can improve COVID-19 survival: A cheap, widely available steroid reduced
deaths by up to one third in severely ill hospitalized patients.
The results were announced Tuesday and the British government
immediately authorized the drug’s use across the United Kingdom for
coronavirus patients like those who did well in the study. Researchers
said they would publish results soon in a medical journal, and several
independent experts said it’s important to see details to know how much
of a difference the drug, dexamethasone, might make and for whom.
But “bottom line is, good news,” said the United States’ top
infectious disease expert, Dr. Anthony Fauci. “This is a significant
improvement in the available therapeutic options that we have.”
The coronavirus outbreak has killed more than 438,000 people worldwide since it began late last year in China.
The study, led by the University of Oxford, was a large, strict test
that randomly assigned 2,104 patients to get the drug and compared them
with 4,321 patients getting only usual care.
The drug was given either orally or through an IV for 10 days. After
four weeks, it had reduced deaths by 35% in patients who needed
treatment with breathing machines and by 20% in those only needing
supplemental oxygen. It did not appear to help less ill patients.
Researchers estimated that the drug would prevent one death for every
eight patients treated while on breathing machines and one for every 25
patients on extra oxygen alone.
“Those are big effects,” said one study leader, Dr. Martin Landray at
Oxford. “It’s not a cure, but it’s certainly a long way forward.” It’s
especially good news that the drug “is remarkably cheap, perhaps $20 or
$30 for an entire course of treatment,” he added.
Steroid drugs reduce inflammation, which sometimes develops in
COVID-19 patients as the immune system overreacts to fight the
infection. This overreaction damages the lungs and can prove fatal. The
World Health Organization and others advise against using steroids
earlier in the course of illness because they can impede clearing the
virus.
“Early on, you’re fighting the virus and you want your immune system
to be as intact as possible,” Fauci explained. But in the advanced stage
of COVID-19, the battle against the virus causes so much inflammation
that it “is hurting you more than helping you,” he said. The results
seen in the Oxford study make “perfect sense” with that notion, he said.
Many hospitals and doctors have been trying steroids to quell the
immune system, but there’s been no evidence from high-quality studies
that it helps for COVID-19.
Although the Oxford researchers talked only about dexamethasone, the
detailed plans for the study say that participating hospitals could use
two other steroids — prednisolone or hydrocortisone — and there’s no
reason to think any particular one works better than another, said Dr.
Francisco Marty, an infectious disease specialist at Brigham and Women’s
Hospital in Boston.
“I assume the majority of people used dexamethasone, but it’s not the
only one that people could have used,” he said. “It will be great to
see the data to see if there’s a class effect.”
Steroids are known to help fight certain fungal and bacterial
infections such as meningitis, and a type of pneumonia common in HIV
patients, but they have not proved useful against flu or some other
viral diseases, he said. The Oxford results would persuade him to try
them for COVID-19 patients needing extra oxygen, he said.
Until now, the only drug shown to help fight COVID-19 is remdesivir,
an experimental drug from Gilead Sciences that blocks an enzyme the
virus uses to copy its genetic material. Remdesivir shortened the time
to recovery for severely ill hospitalized patients to 11 days on average
versus 15 days for those just given usual care, in a study led by the
U.S. National Institutes of Health.
“We don’t know yet” if remdesivir could be used with dexamethasone — or before or after it — to give more benefit, Fauci said.
Even though dexamethasone only helps in severe cases, “countless
lives will be saved globally,” said Nick Cammack, a virus expert at the
Wellcome Trust, a British charity that supports research.
“This is the dream,” because the drug has been used for decades for
other conditions, said Cammack, who had no role in the study. “It’s very
straightforward to make so there’s no reason this can’t be rolled out
for the entire world.”
No information was given on side effects, but researchers said they
used a low dose and for a short time, which is generally safe.
“Short-term low dose shouldn’t be a problem, but steroids do have a
lot of side effects” including weight gain, high blood pressure, water
retention, mood changes, sleep problems and rise in blood sugar for
people with diabetes, Marty said.
Dr. Peter Bach, a health policy expert at Memorial Sloan-Kettering
Cancer Center in New York, noted that in the study 41% of those on
breathing machines and 25% on oxygen alone died.
“The mortality rate seems to be way higher than it is in the U.S.,”
where one recent study found a death rate of 12%, although that was only
after two weeks versus four in the UK study, he said.
“We are going to struggle to look at these data and use them for U.S.
patients,” he said. But he added that “it’s good news for science that
the right studies got done,” and that the drug works and is so
affordable and available.
The Oxford study is the same one that earlier this month showed the
malaria drug hydroxychloroquine was not working against the coronavirus.
The study enrolled more than 11,000 patients in England, Scotland,
Wales and Northern Ireland who were given either standard care or that
plus one of several treatments: dexamethasone; hydroxychloroquine; the
HIV combo drug lopinavir-ritonavir; the antibiotic azithromycin; the
anti-inflammatory drug tocilizumab; or plasma from people who have
recovered from COVID-19 that contains antibodies to fight the virus.
Research is continuing on the other treatments. The research is
funded by government health agencies in the United Kingdom and private
donors including the Bill and Melinda Gates Foundation.
Dr. Stephen Griffin, of the University of Leeds in England, said
treatments that can prevent infection and serious illness are still
needed.
“Ideally, we will find something that stops the disease from
progressing to a more advanced stage,” he said, noting that remdesivir
might yet prove to be effective this way. Dexamethasone “is not a wonder
pill, but it will lessen some of the nasty effects of COVID-19.”
