Q&A: Dexamethasone and COVID-19

It seems there may be some good news for a new treatment for people with severe COVID-19.

According to researchers at the University of Oxford in the world’s largest trial testing existing treatments, a generic steroid drug can significantly reduce deaths of very sick COVID-19 patients, and could point to a new treatment for severe cases.

The commonly used steroid, dexamethasone, is the first drug to show that it could improve the survival of severely ill coronavirus patients.

But what is the drug and how does it work? For more information, we asked Associate Professor Justin Denholm – the Medical Director of the Victorian Tuberculosis Program at Melbourne Health, and Principal Research Fellow at the University of Melbourne’s Department of Microbiology and Immunology and the Peter Doherty Institute for Infection and Immunity.

What is dexamethasone?

Dexamethasone is a kind of corticosteroid medication, similar to prednisolone or cortisone.

It has been widely used around the world since the 1960s, including in Australia, to treat a range of conditions including arthritis, asthma and some skin conditions.

How does it work?

Corticosteroids like dexamethasone are closely related to cortisol, a steroid hormone produced naturally in our adrenal glands.

Cortisol is released in response to stress, including as part of a reaction to significant infection. Corticosteroid medications have a range of effects, which in the context of COVID-19, are most importantly related to reducing inflammation.

Corticosteroids work by decreasing inflammation and suppressing the immune system, as this excess inflammation can damage healthy tissue.

What has it previously been used for?

Very generally, inflammation is the body’s immune system response to an irritant. This could be a foreign object, like a splinter in your finger, or pathogens (germs) like bacteria or viruses – like COVID-19.

In medical practice, corticosteroid drugs are mainly used for reducing this inflammation and swelling.

Dexamethasone is regularly used for some severe infections, including meningitis and some forms of tuberculosis. Corticosteroid medications are also commonly used for treating auto-immune diseases, by reducing the body’s inflammatory response.

This can be especially helpful when swelling is happening in limited spaces in the body, like the brain, joints or lungs.

Why might it be effective in severe COVID-19 cases?

Severe infections like COVID-19 often lead to significant amounts of inflammation, particularly in the lungs.

This inflammation leads to swelling and fluid accumulation, which increases the work of breathing and interferes with the free passage of oxygen through the lungs.

During the COVID-19 pandemic, there have also been reports of fatalities due to an overreaction of the body’s immune system called a cytokine storm.

When the SARS-CoV-2 virus enters the body it triggers an immune response, attracting immune cells to attack the virus, resulting in localised inflammation in the lungs. But in some patients, too many cytokines are released, activating more immune cells which can result in hyper-inflammation.

This ‘overreaction’ in the body can seriously harm or even kill the patient

The use of a steroid like dexamethasone might reduce this inflammation and help people recover more quickly.

However, steroids can also increase susceptibility to some infections; and there has been concern that using steroids in conditions like SARS and COVID-19 might lead to worse outcomes overall.

Many guidelines have so far not recommended using dexamethasone for COVID-19, while they wait for good quality-evidence on what the safest approach might be.

What do the results from this trial tell us about coronavirus?

The RECOVERY Trial, which has been running since March out of Oxford University, is the biggest randomised controlled trial of drugs against COVID-19 in the world. This is the right kind of study to provide this type of useful information.

According to what we know of their results, dexamethasone cuts the risk of death by a third for patients on ventilators. For those on oxygen, it cut deaths by a fifth.

In the trial, around 2,000 hospital patients were given 6mg of the drug daily and then that result was compared with the more than 4,000 who were not.

The results might suggest that reducing inflammation through use of dexamethasone can overall lead to better outcomes in severe COVID-19 cases, including lower risk of death.

But people should not be going out to get a prescription to take at home. The drug doesn’t seem to help people with mild COVID-19 symptoms, only those who are ventilated or need oxygen. And dexamethasone has a range of known side effects that would have to be carefully considered.

Additionally, these results have only been released in a brief summary statement so far.

That’s disappointing; to be able to properly understand what they mean and how practice might change as a result, it’s critical for us all to have access to a properly reviewed and detailed report, rather than a short overview.

Once that information is available, we can use it to consider how it might apply to people here in Australia, and how our hospitals and research programs should best adapt to make sure we’re continuing to provide the best possible care.

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