A rising star in the COVID-19 treatment arena, dexamethasone – a powerful corticosteroid – has stirred excitement among World Health Organization experts and researchers around the world, following the publication of promising early results from the United Kingdom’s Recovery trial. 

In COVID-19 patients only receiving supplemental oxygen, the trial found that dexamethasone reduced mortality by 20%. In patients requiring mechanical ventilation, the drug cut the mortality rate by up to a third.

“We will update our clinical guidance to reflect how and when dexamethasone should be used to treat COVID-19,” announced WHO Director-General Dr Tedros Adhanom Ghebreyesus on Wednesday. “WHO has now started to coordinate a meta-analysis pulling data from several clinical trials to increase our overall understanding of this intervention.”

The cheap drug could become the ‘standard-of-care’ for patients suffering from more severe forms of the disease, Soumya Swaminathan, WHO Chief Scientist, told the Financial Times, echoing comments from Peter Horby, one of the UK trial’s principal investigators. Producers are already poised to ramp up production of the common drug – including Cipla, an Indian generics manufacturer; Aché, the biggest dexamethasone producer in Brazil, and Hikma Pharmaceuticals, a large dexamethasone manufacturer. 

WHO Experts Urge Restraint In Using Dexamethasone

The drug acts as an anti-inflammatory drug, calming the swelling around severely ill patients’ lungs, rather than targeting the virus itself like another promising treatment – the antiviral remdesivir.

“[Dexamethasone] is a very, very powerful anti inflammatory drug. It can rescue patients who are in very serious condition where their lungs and cardiovascular system around their lungs may be very inflamed,” said WHO Health Emergencies Executive Director Mike Ryan. “This possibly allows the patients to continue getting oxygen into the blood from the lungs for a very critical period, or it rapidly reduces inflammation at a critical period in the illness.”

However, the drug has shown to only improve outcomes in patients suffering more serious illness. No benefit was observed in patients who did not require respiratory support, and health experts are urging caution for using the drug.

“This is not for mild cases, this is not for prophylaxis,” clarified Ryan. “It is not a treatment for the virus itself, it is not a prevention for the virus.

“In fact, steroids, particularly powerful steroids can be associated with viral replication in other words they can actually facilitate the division and replication of viruses in human bodies. So it’s exceptionally important that this drug is reserved for use in severely ill and critical patients who can clearly benefit from the drug.”

WHO Hydroxychloroquine Trial Stopped Again

Meanwhile, the much hyped antimalarial drug hydroxychloroquine seems to be fading from favor, as WHO announced they would stop enrolling new patients into the hydroxychloroquine arm of its multicountry SOLIDARITY trial for COVID-19 treatments. New patient enrollment has also been stopped in the hydroxychloroquine arm of France’s DISCOVERY trial, one of the country arms of the larger WHO trial.

The move was prompted by early results released by the United Kingdom’s Recovery trial, which found no reduction in mortality among around 3000 COVID-19 patients taking the drug compared to those receiving standard treatment.

“After deliberations [between investigators from the Solidarity and Recovery trials], they have concluded that the hydroxychloroquine arm will be stopped in the Solidarity Trial,” announced Ana Maria Henao Restrepo, a medical officer in WHO’s Health Emergencies Programme.

“The internal evidence from the Solidarity-Discovery trial, the external evidence from the UK Recovery trial, and the combined evidence from these large randomized trials brought together suggest that hydroxychloroquine, when compared to the standard of care, in the treatment of hospitalized COVID-19 patients, does not result in the reduction of mortality for those patients,” said Restrepo

The move represents another nail in the coffin for hydroxychloroquine, once touted as one of the most promising COVID-19 treatments, following the United States Food and Drug Administration rescinding emergency use approval for the drug on Monday. The hydroxychloroquine arm of the Solidarity trial had just resumed after being paused for 1 week, following the publication of a massive, now retracted, study in The Lancet that claimed patients taking the drug were at higher risk of mortality.

Still, Restrepo emphasized that the move to stop the hydroxychloroquine arm did not “constitute an official WHO policy,” nor does it apply to investigations around the use of hydroxychloroquine as a preventative treatment for COVID-19.

“This is just based on results from the trials. This does not apply to the evaluation of hydroxychloroquine as possible prophylaxis in patients exposed to COVID-19 – that’s a different thing,” clarified Restrepo.

Image Credits: Twitter: @WHO.