A glimmer of hope but...

...dexamethasone's positive effect on patients with severe Covid-19 infection and no effect on mild ones imply that it will not be used on a large scale

There may be a new ray of hope for COVID-19 victims. A well-known, easily available steroid seems to reduce mortality in critically ill patients, according to a controlled trial. The steroid, dexamethasone, was given to over 2,100 patients in the RECOVERY trials in the UK, and they were compared to a control group of over 4,300 patients who were not administered the drug.

This drug significantly reduces mortality, although it is not useful for milder cases. In the trial, it cut mortality rates by about one-third in patients on ventilators and reduced mortality about 20 per cent for patients on oxygen without ventilators.

The RECOVERY group which ran the trials announced the findings in a press release on Tuesday, but they have not yet released a paper. Immediately after the release, the UK government authorised use of dexamethasone for hospitalised patients.

RECOVERY is a large randomised, controlled trial group testing several potential therapies. It is run by the Nuffield Department of Medicine and it’s supported by a grant to the University of Oxford from UK National Institute for Health Research (NIHR). There is core funding from Wellcome, the Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, etc.

RECOVERY has trialled Lopinavir-Ritonavir (commonly used to treat HIV), low-dose Dexamethasone,  Azithromycin, Tocilizumab (an anti-inflammatory) and convalescent plasma (collected from donors who have recovered from Covid-19).

In this study, it administered dexamethasone at six milligrams per day for ten days to 2,104 randomly chosen patients by mouth or injection and compared with 4,321 patients randomised to “usual care”. Among patients who received usual care, mortality within 28 days was highest in those who required ventilation (41 per cent), intermediate in those who required oxygen only (25 per cent), and lowest among those who did not require respiratory intervention (13 per cent).

Dexamethasone reduced deaths by one-third in ventilated patients, and by one-fifth in patients receiving oxygen only, with a statistical confidence interval of 95 per cent. There was no benefit to patients who did not require respiratory support. Overall, dexamethasone reduced the 28-day mortality rate by 17 per cent.

Based on these results and the known mortality rates, one death would be prevented by using this drug for treatment of every eight ventilated patients, and one death would be prevented for every 25 patients requiring oxygen who received this drug.

Dexamethasone is a glucocorticosteroid. Corticosteroids, which are naturally produced by the adrenal gland, find uses such as cancer treatment. These steroids decrease the natural immune response and help reduce swelling and allergic reactions. In India, the drug already sells Rs 100 crore annually. 

Zydus Cadila’s Dexona is the most popular brand, while Wockhardt markets it as Decdan, and Cadila Pharmaceuticals as Dexasone.

The use of steroids to treat viral respiratory infections such as Covid-19 is controversial, and this drug is also known to have major side-effects. Steroids suppress the immune system, which provides relief from patients whose lungs are affected by a violent immune response in severe cases. The trial suggests that the benefits outweigh potential harm. The positive results with severe cases, and no effect on mild cases implies that this will not need to be used except in a relatively small number of critical cases.

The only other drug, which seems to work is the antiviral, remdesivir. In trials, remdesivir shortened the element of hospital stay for most patients but it doesn’t seem to have a significant effect on mortality rates. Remdesivir is also in short supply and hard to administer.

Dexamethasone is found on pharmaceutical shelves worldwide and it can be swallowed in pill form.

Epidemiologists involved in RECOVERY said that it could cost less than £50 to treat eight patients in Britain. The findings also have implications for other severe respiratory illnesses since this may benefit patients with similar symptoms who also suffer from severe immunological responses.

The RECOVERY (Randomised Evaluation of Covid-19 Therapy) group was established to test several potential treatments for Covid-19. Over 11,500 patients have been enrolled from over 175 National Health Service hospitals in the UK.

Peter Horby, professor of emerging infectious diseases in the Nuffield Department of Medicine, University of Oxford, and one of the chief investigators for RECOVERY, says: “Dexamethasone is the first drug to be shown to improve survival. This is an extremely welcome result. Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.”

Unfortunately, this drug will not actually “cure” Covid-19 even though it gives the critically ill a better fighting chance. Research continues across the globe, to try and find a cure, side-by-side with research to develop vaccines.