Steroids improve outcomes for severe COVID-19 infections

Several studies of critically ill patients with COVID-19, published in JAMA: The Journal of the American Medical Association, show that fewer patients died and less intensive care (ICU) support was required when patients received corticosteroids compared with usual treatment. The effect was consistent for those receiving either hydrocortisone or dexamethasone.

One of these studies was the international multicentre REMAP-CAP trial, set up by a group of intensive care and infectious diseases specialists to enable researchers to rapidly analyse the effectiveness of different treatment options for eligible COVID-19 patients admitted to ICU. Led by Professor Steve Webb from Monash University, the investigators began randomising patients with COVID-19 to alternative hydrocortisone dosing strategies compared with patients who received no corticosteroid.

Involving 384 adult participants globally, the researchers found a 93% probability that administration of hydrocortisone improved recovery and survival, including less time on organ support in ICU — especially in patients not yet requiring breathing support with a ventilator. These findings and those of six other studies were combined in a prospective meta-analysis conducted by the World Health Organization (WHO) and are expected to change how doctors treat COVID-19 patients in the ICU.

Dr Colin McArthur, who leads the REMAP-CAP trial in New Zealand and is a co-author of the WHO meta-analysis, said the seven randomised clinical trials showed similar results across patients receiving either hydrocortisone (tested in three trials), dexamethasone (tested in three trials) or methylprednisolone (tested in one trial).

In the analysis involving 1703 patients, the odds of death within four weeks were much lower among patients who received corticosteroids compared with those who received usual care or placebo. Of those randomised to corticosteroids there were 222 deaths and 456 survivors, compared to 425 deaths and 600 survivors of those randomised to usual care or placebo.

“That equates to over 20% fewer deaths,” said Dr McArthur, who added that one extra patient would survive for every 11 treated with corticosteroids.

The evidence from these additional studies reinforces the results of the UK-based RECOVERY trial, which released its findings into dexamethasone in June. As a result of the RECOVERY trial, many hospitals around the world adopted dexamethasone as part of their usual care for severely ill patients with COVID-19, and most ongoing clinical trials of corticosteroids paused recruitment — including those investigating hydrocortisone as a potential treatment.

Dr McArthur said the meta-analysis confirms that hydrocortisone is similarly effective as dexamethasone in treating critically ill patients with COVID-19, and is therefore an acceptable alternative. He said it is important for clinicians to have options, especially if there are drug supply issues, and another advantage of both these treatments is that they are inexpensive.

“I don’t think there’s going to be any question now about corticosteroids being the standard of care,” he said.

With the benefit of corticosteroids now established, Dr McArthur said the REMAP-CAP trial will move on to testing a range of other treatments to further improve the survival rate from COVID-19. Convalescent plasma, anti-coagulation and anti-platelet treatments are planned to be added to the study in New Zealand soon.

Professor Richard Beasley, Director of the Medical Research Institute of New Zealand, said it is remarkable to have strong evidence of a therapy that saves lives within nine months of the disease first appearing. Professor Ian Town, Chief Science Advisor at New Zealand’s Ministry of Health, further welcomed the confirmation of the critical role that corticosteroids play in mitigating COVID-19 impact on lung function.

“We have known for a long time that steroids can help damp down the pulmonary inflammation in a variety of acute situations, so it is very encouraging to see a strong evidence base for their use in COVID-19,” Prof Town said.

Image credit: ©stock.adobe.com/au/Georgiy

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