When the first critically ill COVID-19 patients started arriving in Australian hospitals, intensive care doctors suspected steroids could be an effective treatment.
- New clinical trial data provides further evidence corticosteroid treatments reduce death rates of critically ill COVID-19 patients
- The treatments are already being used in Australia for patients who are severely ill from COVID-19
- National clinical guidelines for corticosteroid treatments will be updated soon in light of the new trial data
Clinical Professor Ian Seppelt from Nepean Hospital in Sydney said intensive care clinicians used steroid treatments but a lack of evidence from clinical trials made them nervous.
“There were all kinds of weird and wacky therapies that had been proposed for a disease that nobody had heard of last December,” he said.
Since then research into corticosteroid treatments for severe COVID-19 patients has advanced quickly.
“We’ve got a new disease, we’ve got a large number of new patients, but we’ve got scientific collaboration to try and get some answers really quickly, and that’s very exciting,” Professor Seppelt said.
Two recent publications have helped firm up the evidence in favour of corticosteroids.
This week a meta-analysis published in the Journal of the American Medical Association (JAMA) found treating critically ill patients with corticosteroids improved survival rates by up to a third.
At the same time the World Health Organization (WHO) updated its guidance to recommend using both dexamethasone and hydrocortisone to treat patients with severe and critical COVID-19.
The meta-analysis examined the preliminary results of seven randomised clinical trials covering three types of corticosteroids: dexamethasone, hydrocortisone, and methylprednisolone.
It found about a third fewer critically ill patients who received the corticosteroids died from COVID-19, compared to those who got usual care or a placebo.
The meta-analysis backed up the findings of a trial by Oxford University researchers that focused on dexamethasone.
The early results of that trial were published in June in pre-print form, meaning it had not yet been peer-reviewed, and was referred to by medical researchers as “Recovery”.
Why are steroids helpful?
Corticosteroids are synthetic drugs that suppress the immune system and decrease inflammation, pain and swelling.
Elena Schneider-Futschik from the University of Melbourne said COVID-19 could cause an immune system “hyper-response” in some patients.
“When you have a severe reaction, your own body attacks itself, and that’s what causes the symptoms and death,” Dr Schneider-Futschik said.
“With corticosteroids, it modulates this immune response, and that is really helpful in treating the patient.”
That doesn’t mean everyone who has COVID-19 should be treated with corticosteroids.
The WHO guidance recommends limiting the treatment to people in hospital with severe and critical illness who are being given oxygen-therapy, and the meta-analysis indicated corticosteroids may increase the risk of death in patients with non-severe COVID-19.
“Corticosteroids suppress the immune system and this is actually negative in the case of a mild infection,” Dr Schneider-Futschik said.
“You want that usefulness of the immune system when it gets rid of infections, but it also helps to protect you from other infections, from other pathogens, for example influenza.”
Are they being used in Australia?
Australia’s National COVID-19 Clinical Evidence Taskforce has recommended the use of dexamethasone for adult patients receiving oxygen, including those on ventilators, since soon after the release of the Recovery trial results.
Professor Steven Webb from Monash University believes the use of corticosteroids is now universal in Australian hospitals.
“It’s certainly my strong expectation there would be no [COVID-19] patient in an ICU in Australia who has not been receiving either dexamethasone or hydrocortisone,” he said.
Professor Webb is leading one of the clinical trials that was included in the new meta-analysis.
The REMAP-CAP trial includes 384 adult patients in 200 ICUs around the world, including in Australia.
It has so far found a 93 per cent probability that treating critically ill patients with hydrocortisone improved their chance of survival and recovery.
Professor Webb said the trial showed both hydrocortisone and dexamethasone had similar effectiveness.
“The public health significance of that is there’s quite a bit more hydrocortisone around than there is dexamethasone, and there had started to be concerns about adequacy of supply of dexamethasone,” he said.
“The results of REMAP-CAP and the meta analysis provide confidence that this is a class effect of all corticosteroids, and not something that was restricted narrowly to dexamethasone.”
The executive director of the National COVID-19 Clinical Guidance Taskforce, Associate Professor Julian Elliott, said the taskforce was likely to amend its recommendations for corticosteroid treatment in coming weeks.
“The data that’s available from the trials that have been recently published will give us more information on other drugs in the corticosteroid class and enable us to update our recommendations,” he said.
What do we still need to know?
Professor Seppelt said intensive care clinicians wanted more data about what doses of corticosteroids were most effective and had the least adverse side effects.
He said the dosage of dexamethasone used in the Oxford University Recovery trial was quite small.
“There’s some data suggesting worse outcomes with much large doses of dexamethasone but there’s an ongoing question about whether 6 milligrams is the right dose or whether different doses might be better,” he said.
Dr Schneider-Futschik said more evidence was needed about which corticosteroids were best for treating severe COVID-19.
“So that’s something where we still need further studies to actually pin down which steroid to use and at what concentration,” she said.