Coronavirus and Steroids: Dexamethasone Promises as a Covid-19 Treatment

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Scientists at the University of Oxford in the UK this week reported that a trial of the drug dexamethasone demonstrates that it may be the first treatment demonstrated to save the lives of Covid-19 patients.

Dexamethasone is a corticosteroid commonly used to treat inflammation. It’s cheap, as low as $ 1 per dose. It has also been around since the 1950s, is disabled for human use, and are available as generics. This makes it an ideal choice for treating severe cases of Covid-19, particularly compared to more expensive, unproven drugs still in the testing phase.

The research team reported that a 6 mg daily dose of dexamethasone reduced deaths by a third in Covid-19 patients on ventilators and reduced deaths by a fifth for patients receiving only oxygen.

“This is a surprising result in a drug, we have a lot of experience,” said Jeremy Faust, an attending physician at the Brigham and women’s Hospital and professor at Harvard Medical School, who was not involved in the study. “He took me by surprise.”

Covid-19 has proven to be a fierce and deadly enemy, with more than 8 million cases and 445,000 deaths reported worldwide as of June 17. But without a proven method of treatment or vaccine, health officials were forced to resort to blunt, expensive tactics like shutting down businesses and staying-at-home orders. Doctors have experimented with a variety of unproven drugs to treat the critically ill. If a drug with evidence behind its effectiveness is good progress.

Another drug, remdesivir, received emergency aid clearance from the Food and Drug Administration to treat Covid-19 based on evidence that it could shorten the length of hospital stays in patients who have recovered from the disease. But dexamethasone is the first drug to reduce the number of victims of the virus.

“This is very welcome,” said Peter Horby, one of the lead investigators and a professor of emerging infectious diseases at the University of Oxford, in a statement. “The survival benefit is clear and great in patients who are sick enough to require oxygen treatment, so dexamethasone should now become the standard of care for these patients.”

The UK National Health Service has already approved the drug. “Starting today the standard treatment for COVID-19: dexamethasone, helping to save thousands of lives while we are dealing with this terrible virus,” UK Health Secretary Matt Hancock said in a press release.

It is also remarkable how quickly researchers have achieved these results, ranging from testing planning, recruiting and testing for results within a few months.

But there are some caveats about these preliminary findings and the way the results were presented.

The dexamethasone study was part of a large randomized controlled trial known as RECOVERY. During the trial, 2,104 randomly selected Covid-19 patients received the drug and were compared to a random 4,321 of patients who received conventional treatments.

The likely mechanism is that dexamethasone modulates the immune system. For people with serious complications from Covid-19, the problem is often not the virus itself, but the collateral damage to the immune response. White blood cells can go into a frenzy and start attacking healthy cells, causing more damage. Covid-19 is also known to trigger an dangerous immune condition known as a cytokine storm which can lead to severe inflammation throughout the body.

Since Covid-19 is a respiratory infection, these effects are often more severe in the respiratory tract. Which can then lead to breathing difficulties that require the use of oxygen or ventilators.

At this late stage of the infection, the stuffing down the immune system can prevent people from getting sick and helping them recover. But at earlier stages of infection, or in milder cases, dexamethasone does not seem to have much effect. The researchers found that it had no impact on patients who were not using supportive breathing.

Because it inhibits the immune system, it could also backfire if prescribed in an early stage of a Covid-19 infection, leaving a patient vulnerable to viruses or other pathogens. It is only in critically ill patients that these compromises can be worth it.

There are also side effects. Dexamethasone can cause dizziness, irregular heartbeat, and psychiatric conditions such as anxiety and suicidal thoughts.

Doctors and other public health experts have also criticized the way the researchers shared their results with the public.

Instead of releasing paper or even a project along a peer review, they summarized the results in a press release. The scientists behind the trial said they wanted information about their results as soon as possible, but without the release of their data, it is impossible for other scientists to scrutinize them. Observers are puzzled why the research team does not have more solid information.

For example, clinicians like Faust want to know about the demographics of the group trial, what drugs the patients were using, and how the researchers set thresholds for serious illness. Doctors need this information to understand how dexamethasone will play out in their own patients.

“As an observer, it’s frustrating because if they have this information available [about lowered fatality rates from dexamethasone]there’s also a lot of other information they could share too, ”Faust said. “At the moment, it is impossible to know if I had a patient in front of me, if the patient in front of me corresponds to a typical patient described by this trial.”

While Covid-19 is spreading rapidly and the world is in desperate need of answers, hasty reporting can be misleading and dangerous. Some preliminary Covid-19 research has been criticized for promoting results that have been dictated by methods, such as a pair of California serological surveys, which discovered the virus was much more prevalent than previously reported before. Even prestigious newspapers like the Lancet and the New England Journal of Medicine had to retract processing documents for Covid-19.

Some public officials, including the President of the United States, have made the anti-malaria drug hydroxychloroquine as a treatment for Covid-19 on fragile preliminary studies. Later, research showed that the drug, at best, has very little and, at worst, could actually kill more patients. The Food and Drug Administration has revoked its emergency use authorization for hydroxychloroquine this week.

This is why it is so important to see the actual numbers and methodology behind the study dexamethasone. “It’s a huge deal or a huge disappointment,” Faust said.

The research team behind the RESUME of the trial has promised to make the data behind their results available to researchers and government regulators as soon as possible.


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