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Exotics hog the headlines but it's an old workhorse that has done the COVID-19 job

One year on, US hospital doctors say the best and most reliable drug for COVID-19 is cheap, familiar, and has all the glamour of an aspirin, writes MedicalBrief. And in the UK, the drug — dexamethasone — has been described as "one of the most dramatically successful outcomes" so far in the battle against the pandemic.

It is now estimated that the discovery of the effectiveness of the drug dexamethasone has saved around 650,000 lives across the world, according to Professor Martin Landray, a founder of the RECOVERY programme – Randomised Evaluation of COVID-19 Therapy – the world’s largest randomised COVID-19 drugs trial.

And one year into the COVID-19 pandemic, hospital physicians in the United States say the best and most reliable drug for the illness is cheap, familiar, and has all the glamour of a Bayer aspirin, writes Randy Dotinga for MedPage Today. He describes dexamethasone as "the steroid workhorse that's been around longer than most of the doctors who prescribe it".

"I love the irony that one of the cheapest medications that exists is one of the only ones that has shown any benefit," said University of California San Francisco hospitalist Charlie Wray, in an interview with MedPage Today.

Physicians say dexamethasone shows more benefit than drugs that have made a splash in the media such as remdesivir and convalescent plasma. However, they warn about dexamethasone's infamous side effects, which can be especially common in the older patients most prone to severe cases of COVID-19, and they urge caution about its use in patients who don't yet need oxygen.

Corticosteroids weren't always the hot drug for COVID. In the early days of the pandemic, "there was a big outpouring of 'don't use steroids' because there was literature from SARS and MERS that found patients who got steroids had higher viral loads," recalled critical care pharmacist Michael Sirimaturos, of Houston Methodist Hospital.

"But then we started getting more and more patients and realising they weren't getting any better. They were in the hospital for 2-3 weeks, and they started showing classic signs of acute respiratory distress syndrome." So the hospital changed course and started administering steroids and saw a significant impact.

An influential study in the New England Journal of Medicine in July 2020 supported use of dexamethasone. It found that 28-day mortality was reduced among patients on oxygen alone or a mechanical ventilator.mOn the other hand, death rates were higher when the drug was given before oxygen supplementation relative to standard care.

"If you look at the treatments we have for COVID — remdesivir, convalescent plasma, dexamethasone — the only one shown to have a mortality benefit is dexamethasone" said Wray. "Convalescent plasma doesn't really work. Remdesivir shortens hospital length of stay, which is a nice thing to do," but doesn't affect mortality.

The National Institutes of Health's guidelines about steroids and COVID notes that "if dexamethasone is not available, alternative glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone can be used."

Physicians agree that the drug in general should be given when patients are on supplemental oxygen or earlier in some cases. "If you've got a very sick individual in front of you, you should have a low threshold to start steroids if the patient is deteriorating," Wray said. "If you're ever in doubt, I would give steroids."

Some patients with underlying disorders such asthma and COPD may already be on steroids before they need oxygen therapy, and they should get their doses increased, one hospitalised told MedPage Today.

At the University of Minnesota, the protocol is to start dexamethasone in COVID-positive patients who are hypoxic (<90% on room air) and stop it when the patient is no longer hypoxic or at discharge. The NIH says dexamethasone "should be continued for up to 10 days or until hospital discharge, whichever comes first."

Sirimaturos agreed that it's important to not keep patients on steroids indefinitely. "You should see a benefit within the first 3-4 days. Maybe reevaluate 4-5 days in…"

Dexamethasone is notorious for its behavioural side effects. such as steroid-induced psychosis or altered mental status is quite common, especially in older adults. "If it occurs, you can try reducing the dose and making their daily routine as similar to normal as possible – awake in daytime and asleep at nighttime. You can try other medications as needed as that might help, a hospitalist told MedPage Today.

The Observer  Science Editor Robin McKie writes that dexamethasone "remains one of the most dramatically successful outcomes in the battle against COVID-19" and  "demonstrates the power of large-scale randomised trials in pinpointing effective medicines" and will be followed, early in 2021, with results from another handful of promising treatments being studied as part of the RECOVERY programme.

These medicines, which could be crucial in the fight to contain COVID-19 next year, are: convalescent plasma, taken from recovering Covid patients; monoclonal antibodies, made by Regeneron; two anti-inflammatory drugs, tocilizumab and colchicine; and aspirin. All are undergoing trials carried out by thousands of doctors and nurses on tens of thousands of patients in hospitals across Britain. First results are expected in January or early February.

So far, RECOVERY has pronounced on four medicines: azithromycin, an antibiotic; the drug combination lopinavir-ritonavir; hydroxychloroquine, a treatment for malaria and rheumatic diseases; and dexamethasone. Only the last saved lives or aided recovery.

In the pipeline:

Convalescent blood plasma is taken from those recovering from Covid-19 and has antibodies that may help others fight infections. Widely used in the US though scientists don’t yet know if it works or who would benefit most from it. The Recovery programme should have answers in a few weeks.

Monoclonal antibodies are artificial antibodies made by the US biotech company Regeneron and were used to treat Donald Trump. It is not yet clear at which stage of illness they should be administered.

Tocilizumab is an anti-inflammatory arthritis drug thought to hold considerable promise, though its exact benefits are unknown. It is also costly.

Colchicine is another promising anti-inflammatory drug; often used to treat gout.

Aspirin is a blood-thinning agent which could help reduce blood clots in the lungs – a worrying complication in some Covid-19 cases.

 

[link url="https://www.theguardian.com/world/2020/dec/27/the-breakthough-medicines-that-could-change-the-course-of-covid"]Full The Observer article[/link]

 

[link url="https://www.medpagetoday.com/infectiousdisease/covid19/90327"]Full MedPage Today article (Registration required)[/link]

 

See also from MedicalBrief Archives:

[link url="https://www.medicalbrief.co.za/archives/update-on-the-recovery-trial-aspirin-added/"]Update on the RECOVERY trial – November 2020[/link]

 

[link url="https://www.medicalbrief.co.za/archives/sa-in-favourable-position-to-roll-out-dexamethasone/"]South Africa in a favourable position to roll out dexamethasone[/link]

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