Dexamethasone is a corticosteroid which has recently been evaluated in clinical trials in the United Kingdom for patients who become seriously ill with COVID-19. These were patients on ventilators where inflammation is associated with a significant risk of not surviving the infection.

Dexamethasone is an affordable treatment to reduce inflammation in these patients and available in several different formulations. The study is significant as it demonstrates how this cost-effective intervention can potentially impact globally on the number of deaths caused by COVID-19.

The study also indicated that there was no benefit for COVID-19 patients who didn’t require ventilation and so it must be stressed that dexamethasone does not represent a treatment to prevent or treat COVID-19 infection. Its value lies specifically as a rescue therapy for those who might otherwise not recover from more severe complications associated with the infection.

This is the first study that I have seen in which I am genuinely excited by the outcomes for patients with severe COIVD-19. Dexamethasone is an older steroid which generally is not used in clinical practice as newer generations of steroids with fewer side-effects are available. However, as an older drug it is off patent which makes it an extremely cheap medication, and importantly available worldwide, and as such had the potential to radically change the nature of COVID-19 treatment. Interestingly this is not the first study to show benefits of steroids in patients with COVID-19. A much smaller study with a different steroid, methylprednisolone, also found benefits.

Overnight, an important result from a large randomized control trial in the UK (RECOVERY) was released on Dexamethasone, a cheap and readily available steroid treatment, for COVID-19. In over 2,000 recruited patients, it showed the Dexamethasone treatment regimen reduced death by one third in ventilated patients in ICU, one fifth in patients requiring oxygen support but none in patients without oxygen support (non severe COVID-19 infection).

While we are awaiting the full report, the preliminary results indicate a significant reduction in mortality for patients predominantly in ICU. This is the first report demonstrating that a drug can significantly increase survival for critically ill COVID-19 patients. Overall this is an important and significant result that in my view is likely to save lives. Given these results and pending confirmation it wouldn’t be surprising to me if Dexamethasone treatment will be quickly adopted as a standard of care for severe COVID-19 patients hospitalised in ICU.

These new findings come from the Oxford-led RECOVERY trial testing possible treatments for hospitalised patients with COVID-19. Treatment with low dose (6 mg) dexamethasone for 10 days significantly reduced the death rate (after 1 month) in people with severe COVID-19 who needed oxygen or use of a ventilator. While not a COVID-19 cure, this is very important step to guide the approach to management of people with the severest forms of lung complications arising from this coronavirus infection. Importantly, these results confirm the important role of corticosteroids in managing people with COVID-19, which had been the subject of debate.

A key feature is that the findings come from a high quality trial with a rigorous study design, appropriate controls and a significant sample size (over 2000 received dexamethasone) drawn from across 175 UK hospitals providing confidence in the results. The results presented today are a preliminary summary of key findings and researchers will be keen to review the peer review publication to critically analyse the details, confirm the rigour of the study and also explore boarder issues of potential harmful effects of dexamethasone to see how the results can be translated into clinical care of critically unwell people with COVID-19.

Infection with SARS-COV-2 can lead to severe respiratory symptoms with some patients ending up on ventilators to assist their breathing; many of the people who go onto ventilators do not recover. Cytokine release syndrome, popularly known as a “cytokine storm”, where the body’s immune system overreacts to the viral infection is thought to be responsible. Drugs aimed at calming this “storm” are being investigated.

The news from the UK RECOVERY trial that a known immunosuppressant, dexamethasone, reduced death in a third of people of ventilators is very welcome. Dexamethasone is a well-established drug, low cost, with a known safety profile and its use could be implemented rapidly. However there are a number of cautions. So far we only have press releases to go on, the actual study data have not been released so this needs to be examined carefully.The retracted Lancet paper on hydroxychloroquine has taught us that lesson.

Also, it was only effective in people who needed ventilation support, dexamethasone was of no benefit to those not on breathing support. As well, because dexamethasone is a powerful anti-inflammatory and immune suppressant, it still must be used with care. Finally, we must be very clear that dexamethasone, if it proves to be as useful as the press release claims, is not a preventative or general treatment, but is only for the most severe cases of COVID-19 that require respiratory support. This in itself is good news, but it must not be exaggerated.

The findings from this study in the UK show that the use of a 10-day course of a corticosteroid called dexamethasone reduced the 28-day mortality in certain hospitalised patients with COVID-19. Specifically, dexamethasone reduced the mortality rate by 1/3 in ventilated COVID-19 patients and by 1/5 in COVID-19 patients requiring any oxygen support.
 
This is important because it was the strongest type of study (a randomised controlled trial), and the first of its kind to show that a drug could reduce the death rate from COVID-19 in hospitalised patients. Also, dexamethasone is a commonly used medication that has been around for decades; therefore, its safety profile is already known. It is also widely available and relatively cheap.
 
Dexamethasone has anti-inflammatory properties; therefore, its beneficial effect in people who are critically ill with COVID-19 supports the evidence that severe COVID-19 is a hyperinflammatory state where an overactive immune system causes a lot of damage to a person.
 
In the study, dexamethasone didn't reduce the 28-day mortality rate in hospitalised COVID-19 patients with a milder illness not requiring oxygen support; however, this doesn't mean that it may not have a benefit if a different end-point is studied e.g. if you examine the time to full recovery from COVID-19 in a group taking dexamethasone or prednisolone for a 7-day period. But this would need to be done under the auspices of a carefully observed randomised controlled trial.

Dexamethasone is a low-cost corticosteroid drug used as an anti-inflammatory in many medical conditions including Crohn’s disease and rheumatoid arthritis. The University of Oxford has been trialling dexamethasone as a treatment for COVID-19 as part of their RECOVERY randomised controlled trial (RCT).

This part of the trial was stopped early because of the improved survival of patients receiving dexamethasone. Dexamethasone reduced deaths by one-third in ventilated patients and by one fifth in patients receiving oxygen compared to those not receiving the treatment. However, there was no benefit for those patients who did not require help with breathing. This is the first large, well-conducted RCT to demonstrate a successful treatment that improves survival in COVID-19 patients. As such it has been welcomed by WHO, and should now become the standard treatment for all hospitalised COVID-19 patients requiring help with breathing.

So far all we have to go on is the press release, which certainly suggests a benefit to dexamethasone in these patients, but until we see the actual data it is impossible to make a meaningful assessment. One of the problems in this pandemic has been the very rapid 'news cycle' where results have sometimes been released prematurely without proper review, and sometimes leading to major embarrassment such as the recent publication and subsequent retraction of a large hydroxychloroquine dataset. The RECOVERY trial is a well designed trial being conducted by a very high quality team, and I am confident robust data will be published as soon as feasible.