What is dexamethasone and how could it save coronavirus sufferers?

CARDIFF, UNITED KINGDOM - JUNE 16: A close-up of a box of Dexamethasone tablets in a pharmacy on June 16, 2020 in Cardiff, United Kingdom. Results of a trial announced today have shown that Dexamethasone, a cheap and widely used steroid drug which is used to reduce inflammation, reduced death rates by around a third in the most severely ill COVID-19 patients who were admitted to hospital. Researches have predicted 5,000 lives could have been saved had the drug been used to treat patients in the UK at the start of the pandemic.(Photo by Matthew Horwood/Getty Images)
The steroid dexamethasone reduced COVID-19 deaths by a third in ventilated patients. (Getty Images)

A potentially life-saving coronavirus drug is being used in hospitals throughout the UK following highly encouraging trial results.

Scientists from the University of Oxford announced on 16 June the low-cost steroid dexamethasone cut the risk of death by one third in patients on ventilation for the respiratory disease COVID-19.

Early research suggests the coronavirus is mild in four out of five cases, however, it can trigger COVID-19.

Had dexamethasone been used at the start of the UK’s outbreak, up to 5,000 lives could have been saved, according to the Oxford team.

What evidence is there dexamethasone works?

The Oxford scientists set up the RECOVERY trial in March to test potential COVID-19 treatments on more than 11,500 patients across 175 NHS hospitals.

More than 2,100 patients received dexamethasone for 10 days, with the results being compared against over 4,300 people on usual care.

COVID-19 had no “set” treatment. Supportive care, like ventilation, was offered while a patient’s immune system worked to naturally fight off the infection.

Dexamethasone was found to reduce deaths by a third in ventilated patients 28 days after it was administered.

Fatalities went down by a fifth in those receiving oxygen.

Dexamethasone did not benefit the patients who were not on respiratory support.

Based on these results, the drug would statistically prevent one death in every eight ventilated patients on dexamethasone, which can be given orally or intravenously.

One fatality would also be warded off in every 25 patients given the treatment while on oxygen.

“Although this appears a relatively modest effect on outcome, for ventilated patients the NNT (number needed to treat) of eight is better than almost any other intervention studied in patients on ventilators for any disease,” said Professor Duncan Young, from the University of Oxford.

Half of all COVID-19 patients who end up on a ventilator do not survive.

Sir Patrick Vallance, the government’s chief scientific adviser, called the results “tremendous news” and “groundbreaking in our fight against the disease”.

How does dexamethasone work?

Dexamethasone is a steroid, which reduce inflammation by mimicking anti-inflammatory hormones.

The coronavirus itself can trigger inflammation.

A patient’s immune system may also go into overdrive, leading to a “cytokine storm” – which occurs when excessive amounts of the immune-fighting proteins cytokines are released.

Some inflammation is good because it helps fight off an infection. A cytokine storm, however, can lead to a dangerous amount of internal swelling.

Dexamethasone is thought to calm this effect, but only in severe cases. Dampening the immune response in milder patients is not thought to be beneficial.

“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,” said Professor Peter Horby, a chief investigator on the RECOVERY trial.

How available is dexamethasone?

Dexamethasone is already used to treat inflammatory conditions, like asthma or severe allergic reactions.

It is also prescribed for disorders caused by an overreaction of the immune system, such as rheumatoid arthritis.

Anticipating the RECOVERY trial would be a success, the UK government reportedly stockpiled enough of the drug to treat 200,000 people.

Health secretary Matt Hancock told the Commons that 240,000 doses of the drug are “in stock and on order”.

In the UK, dexamethasone costs £5.40 ($6.76) a day per patient, with the treatment regimen lasting up to 10 days.

First produced in 1957, the drug is out of patent. This allows lots of different pharmaceutical companies to make and distribute it around the world.

“Dexamethasone is inexpensive, on the shelf and can be used immediately to save lives worldwide,” said Prof Horby.

The Department of Health and Social Care has said dexamethasone is on the government’s parallel export list, which bans companies from buying medicines meant for UK patients and selling them on for a higher price elsewhere.

Does it have any side effects?

In the RECOVERY trial, the patients on dexamethasone were given 6mg once a day.

Professor Chris Whitty, England's chief medical officer, has said there were “no excess harms identified in using this dose in this patient population”.

Nevertheless, dexamethasone has been linked to anxiety, insomnia, weight gain and fluid retention.

In rare cases, it can cause eye disorders, blurred vision and haemorrhages.

The artistic director of the Canal Theatres, Blanca Li attend the reopening of the Canal Theatres after the coronavirus strike. The season begins with the Madrid en Danza festival, which will be held from 17 to 28 June  in Madrid, Spain, on June 17, 2020.  (Photo by Oscar Gonzalez/NurPhoto via Getty Images)
A woman wears a mask in Madrid. (Getty Images)

Are we getting excited too soon?

The RECOVERY trial announcement was only preliminary results, with the study yet to be published in a peer-reviewed journal.

While it may sound like the study was hurried to meet the demand for a COVID-19 drug, many scientists have praised the speed at which it was carried out.

“To see these results in such a short period of time is an incredible scientific achievement,” said Dr Nick Cammack, from the Wellcome Trust.

“The data will give researchers around the world a better understanding of why the drug is effective in these patients.

“This is extremely promising news and a significant step forward, but we still have a long way to go.

“To end this pandemic, we still need better diagnostics to detect, medicines to treat and vaccines to prevent COVID-19.”

Dr Stephen Griffin from the University of Leeds called the study “of tremendous importance”.

Nevertheless, he wants to see further trials that investigate the potential of the treatment, “perhaps through the combination of low-dose dexamethasone with other inflammatory mediators, or with virus-targeted therapies, such as remdesivir”.

An anti-malarial drug, remdesivir appears to speed up COVID-19 recovery time. It is administered as an infusion, rather than a tablet.

As a new drug, remdesivir supplies are expected to be limited and its price high.

Speaking of dexamethasone, Dr Ayfer Ali, from Warwick Business School, added: “Remember it is not a cure for all, just one more tool; but this shows the potential of drug repurposing”.

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