Results from a clinical trial led by University of Oxford researchers in the UK show that dexamethasone, a commonly used, low-cost steroid, can reduce deaths in critically ill COVID-19 patients that require ventilation or oxygen support. The corticosteroid is being hailed as an actual game changing, breakthrough treatment for COVID-19.
Dexamethasone is used to treat conditions such as arthritis, asthma, disorders associated with blood, hormones and the immune system, allergic reactions, some skin and eye conditions, certain bowel conditions as well as some cancers.
Preliminary results released from the trial show that the drug was able to reduce the number of deaths by almost one third in severely ill COVID-19 patients on ventilators, but demonstrated no significant effect in mild cases of the infection. With this, dexamethasone becomes the first drug shown to reduce mortality in the sickest subset of COVID-19 cases.
The UK study is a randomized controlled clinical trial called RECOVERY (Randomised Evaluation of COVid-19 thERapY) in which potential treatments for COVID-19, including low-dose dexamethasone, are being assessed. The trial enrolled over 11,500 patients from over 175 National Health Service (NHS) hospitals across the UK since March 2020, which is when the trial was initiated. As of June 8, patient recruitment to the dexamethasone arm was stopped as a sufficient number of patients had been enrolled to establish whether or not the drug had a meaningful benefit, according to the trial Steering Committee.
Results of the RECOVERY trial were released on June 16 in a press release.
In the trial, 2,104 participants received dexamethasone, either orally or by intravenous injection, at a low dose of six milligrams per day for ten days, while 4,321 participants were randomized to standard of care alone. Among those who received standard of care, it was reported that 28-day mortality was highest in those who required ventilation (41 percent), intermediate in patients who required oxygen only (25 percent) and lowest among those who did not require any respiratory assistance (13 percent).
Dexamethasone reduced deaths by one third in ventilated patients and by one fifth in patients who only received oxygen. No benefit was seen in patients who did not need any respiratory support. In other words, these results indicate that dexamethasone treatment would prevent one death in about eight ventilated patients, or one death in 25 patients who require oxygen alone.
Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford and one of the chief investigators for the trial said in the press statement, “Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result. 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. Dexamethasone is inexpensive, on the shelf and can be used immediately to save lives worldwide.”
Dexamethasone and Inflammation
The severity of COVID-19 is often due to respiratory complications that arise when the immune system goes into overdrive, producing large amounts of inflammatory cytokines to cause the condition of ‘cytokine storm.’ Given this, the effectiveness of dexamethasone is not surprising as the drug is a steroid that acts to reduce inflammation.
Steroids can improve the condition of patients whose lungs are attacked by an overactive immune response to potentially cause Acute Respiratory Distress Syndrome (ARDS). Despite this, treatment guidelines from health agencies in many countries have warned against treating coronavirus-infected people with steroids because they act to suppress the immune system. This is obviously not ideal in an infection situation where a person would need functional immunity to fight off the virus,
However, the use of low doses of dexamethasone in the RECOVERY trial appears to offer greater benefit than harm. Study investigators said that they found no outstanding adverse events from the treatment. “This treatment can be given to pretty much anyone,” said Horby.
Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford and one of the chief investigators on the study said, “Since the appearance of COVID-19 six months ago, the search has been on for treatments that can improve survival, particularly in the sickest patients. These preliminary results from the RECOVERY trial are very clear – dexamethasone reduces the risk of death among patients with severe respiratory complications. COVID-19 is a global disease – it is fantastic that the first treatment demonstrated to reduce mortality is one that is instantly available and affordable worldwide.”
Dexamethasone Added to Standard of Care in Some European Countries
The UK’s NHS has gone ahead and announced that dexamethasone will now be added to the standard of care for COVID-19 treatment. “It’s very, very rare that you announce results at lunchtime, and it becomes policy and practice by tea time, and probably starts to save lives by the weekend,” said Landray.
Interestingly, Science magazine has reported that in Spain, dexamethasone was already in widespread use for treatment of COVID-19. In a paper published in the journal Lancet Respiratory Medicine, Carlos Ferrando, an anesthesiologist at the Hospital Clinic of Barcelona, and his colleagues showed that the drug decreased mortality in patients with ARDS who were not infected with COVID-19.
With the increasing numbers of COVID-19-infected people who arrived at the hospital in subsequent weeks, Ferrando began a randomized clinical trial to test dexamethasone in the patients. The study was limited by a small placebo group as most received the steroid treatment. Ferrando is currently analyzing data from thousands of COVID-19 patients who were in ICUs across the country, with about 80 percent of them having had received steroids. “It seems like we have a signal that those corticoids decrease mortality, but we need to finalize the analysis,” said Ferrando.
The World Health Organization (WHO) has also welcomed the preliminary results from the UK RECOVERY trial. “This is the first treatment to be shown to reduce mortality in patients with COVID-19 requiring oxygen or ventilator support,” said Dr. Tedros Adhanom Ghebreyesus, WHO Director-General. “This is great news and I congratulate the Government of the UK, the University of Oxford, and the many hospitals and patients in the UK who have contributed to this lifesaving scientific breakthrough.”
While the antiviral drug is the only other drug that has received regulatory approvals for treatment of the novel coronavirus infection, it has only been shown to reduce recovery and hospitalization times in severely ill patients – unlike dexamethasone, it does not reduce mortality.
The steroid treatment may thus improve outcomes for people who become severely ill from COVID-19, many of whom have underlying health conditions that make them more susceptible to complications from the COVID-19-causing SARS-CoV-2 virus.