A randomised, controlled clinical trial headed by the University of Oxford has found a widely available and inexpensive steroid to improve survival in COVID-19. Dexamethasone, the corticosteroid in question, is the first treatment shown to significantly diminish the risk of dying from the coronavirus (SARS-CoV-2) responsible for more than 42,200 deaths in the UK alone. During the trial, 2104 COVID-19 patients were randomly selected to receive dexamethasone and compared with 4321 patients receiving usual care. The only other drug demonstrated to benefit COVID-19 treatment is remdesivir; a broad-spectrum antiviral medication previously used to treat Ebola. However, despite shortening the recovery time of hospitalised COVID-19 patients in a similar trial, remdisivir did not significantly affect mortality. In contrast, low doses of dexamethasone cut deaths in ventilated patients by one-third, whilst reducing mortality by 20% in those only requiring oxygen. No benefit was observed among patients with milder COVID-19 cases where respiratory support was not required. Nevertheless, according to Peter Horby, one of the trial’s Chief Investigators and Professor of Emerging Infectious Diseases at Oxford University, the above findings still represent “a major breakthrough.” Indeed, according to these preliminary results, dexamethasone treatment could save one life for every eight ventilated patients or one for every 25 only needing oxygen. Furthermore, if such a treatment was used in the UK from the beginning of the pandemic, up to 5,000 lives could have been saved, researchers claim. Although announced in a press release on 16 June, given the widespread importance to public health researchers are working hard to publish the results in full as quickly as possible. The absence of the study’s full details has not prevented the UK government authorising the use of dexamethasone for hospitalised COVID-19 patients requiring oxygen or ventilation, however. 200,000 courses of the drug are currently in the NHS’s stockpile and according to Prime Minister Boris Johnson, steps have been taken to “ensure we have enough supplies, even in the event of a second peak.” According to Professor Landray, another of the trial’s chief investigators, though appropriate hospital patients should be given this treatment “without delay”, individuals should not purchase the drug themselves to take at home.
Fortunately, unlike remdesivir, dexamethasone is neither a new drug nor in short supply. In fact, it is common to pharmaceutical shelves across the world, being used since the early 1960s to treat various conditions, such as rheumatoid arthritis, due to its inflammatory properties. Dexamethasone can be given intravenously in intensive care situations but typically comes in pill form, thus is easy to administer. A benefit additional to its wide availability and highly welcome in light of the increasing coronavirus infection rates in countries with limited healthcare access.
The dexamethasone study forms part of the RECOVERY trial, a UK-based investigation testing potential treatments for hospitalised COVID-19 patients. Since launching in March, over 11,500 individuals across 175 hospitals have been enrolled, making it one of the world’s largest randomised controlled trials for coronavirus treatments. The malaria drug hydroxychloroquine was also examined, however, although heralded by the US President, was withdrawn from the study after evidence that it did not produce an antiviral effect.
It appears dexamethasone helps prevent some of the damage resulting from hyperactivation of the immune system upon infection by SARS-CoV-2 in some patients; a potentially deadly over-reaction known as a cytokine storm. The use of such immunosuppressive drugs in the trial was, however, controversial. In the early stages of the pandemic, multiple international guidelines strongly discouraged taking steroids for COVID-19. This was due to fears that dampening the immune system would exacerbate the disease and prolong infection. Furthermore, the use of steroids as treatment for other coronaviruses, SARS and MERS, provided mixed results; although such may have been due to the inadequate size of these trials. The positive results for dexamethasone are, therefore, not only surprising but reinforce the importance of large-scale randomised control trials.
Despite lockdown’s slight relaxation, an end is not yet in sight. Nevertheless, dexamethasone provides at least a little light within the current darkness of uncertainty.
Edited by Lizzy Aiton.