Cheap, widely available steroids significantly reduce the risk of death for severely ill COVID-19 patients, according to a new international study that reinforces the findings of an earlier British trial and confirms that more than one type of steroid can save lives.
The new findings prompted the World Health Organization to update its treatment guidelines, bringing the international agency’s advice into line with that of many countries, including Canada, that already recommend a steroid called dexamethasone for the sickest COVID-19 patients.
The drug, which has been used to treat other illnesses for decades, burst into the public consciousness in June, when a British clinical trial found it cut the risk of death by about a third for COVID-19 patients on mechanical ventilators.
The new study, published on Wednesday in JAMA, pooled data from the British trial and six other clinical trials – including one with Canadian sites – and confirmed that dexamethasone did indeed cut the risk of death substantially for coronavirus patients in the intensive-care unit, even those who did not require invasive ventilation.
The study found that a related steroid, hydrocortisone, also worked, which should help alleviate concerns about shortages of dexamethasone.
Srinivas Murthy, an infectious-disease physician at BC Children’s Hospital and one of the authors of the new meta-analysis, said he was “thrilled” to see steroids emerge as an early success story in the treatment of severe COVID-19, because the drugs are inexpensive, easy to get and have a long safety record.
“It’s the best news, I think, that we’ve had in this pandemic so far,” Dr. Murthy said.
Still, steroids are far from a silver bullet for COVID-19. The British trial, called RECOVERY, found dexamethasone made no difference for less-sick patients who weren’t on respirators. In fact, the new WHO guidance, also released on Wednesday, discouraged giving steroids to patients with mild versions of the coronavirus disease.
However, among participants in the British trial who were on ventilators, 29 per cent of those receiving dexamethasone died compared with 41 per cent of those receiving usual care – a 30-per-cent reduction in the relative risk of death.
“I think a lot of us looked at that RECOVERY data and thought, ‘I’ve never seen anything that big. Is this really plausible?’” said John Marshall, a critical-care physician at St. Michael’s Hospital, part of Unity Health Toronto, and the co-chair of a WHO working group looking at best ways to care for coronavirus patients.
“We thought it was important that we validate that this existed in other populations before people started using corticosteroids indiscriminately in patients,” he said.
But when it came to further studying steroids in COVID-19 patients, there was a hitch. The early findings of the RECOVERY trial – which has generally been praised for its size and rigour – prompted many randomized control trials to stop enrolling new patients and give dexamethasone to all COVID-19 patients in the ICU.
The Canadian arm of one of those trials was led by Dr. Marshall, who is also a senior researcher at the Li Ka Shing Knowledge Institute at St. Michael’s.
Rather than see the findings of the partly completed trials go to waste because they did not recruit enough participants, researchers pooled data from the seven trials conducted in 12 countries, including Brazil and France, that included 1,703 critically ill COVID-19 patients.
Their findings bolstered the conclusions of RECOVERY, Dr. Marshall said. The pooled analysis found that 40 per cent of critically ill patients who received standard care died compared with 32 per cent of those who received steroids.
Dr. Marshall said it is important that the additional studies in the new analysis included countries not as well off economically as Britain, because it shows that the RECOVERY results can be achieved in places without state-of-the-art medical facilities and universal publicly funded health care.
“We wanted a broader geographic sweep,” he said.
The results of the pooled analysis, three other related studies of steroids in COVID-19, and an editorial endorsing their use in critically ill coronavirus patients were published in JAMA.
Although it’s not entirely clear how steroids improve outcomes in these patients, they are thought to reduce inflammation and the overreactive immune response that the body sometimes mounts as it tries to fight off SARS-CoV-2, the virus that causes COVID-19.
Rob Fowler, a critical-care doctor at Toronto’s Sunnybrook Health Sciences Centre who helped write Canada’s guidance for managing COVID-19 patients, agreed the latest research on steroids was good news, but warned against losing sight of the “big picture” in the pandemic.
“We’re chipping away, importantly, at improving outcomes,” said Dr. Fowler, who was not an author on any of the new JAMA studies, but did help with data monitoring of the RECOVERY trial. “We don’t have a medication that works most of the time for most people. Preventing exposure [to the coronavirus] is the most important thing we can do so far.”
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