Dexamethasone could benefit certain hospitalized COVID-19 patients

The RECOVERY Collaborative Group has released a preliminary report describing the effects of dexamethasone treatment among patients hospitalized with coronavirus disease 2019 (COVID-19).

Preliminary results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial showed that dexamethasone reduced 28-day mortality among patients who required invasive mechanical ventilation and those who required oxygen.

However, no such benefit was observed among hospitalized patients who were not receiving respiratory support.

Peter Horby (University of Oxford) and collaborators recommend that guidelines still stating that corticosteroids are either contraindicated or not recommended as a treatment approach to COVID-19 should now be updated, as have guidelines in the UK.

According to the group, dexamethasone is an effective treatment for the most severely ill COVID-19 patients, and its low cost, wide availability, and robust safety profile mean it could be used worldwide.

A pre-print version of the paper is available in the server medRxiv*, while the article undergoes peer review.

Susceptibility to severe respiratory problems among older people

Although COVID-19 is generally associated with asymptomatic or only mild disease, a vast proportion of older people who become infected develop severe respiratory complications that require hospitalization.

These patients can develop respiratory failure and then require prolonged respiratory support.

In the UK, the mortality rate among hospitalized COVID-19 patients is more than 26%, and among those that require invasive mechanical ventilation, this figure rises to more than 37%.

Although remdesivir has been shown to accelerate the time to recovery among hospitalized patients, no treatment has yet been shown to lower the mortality rate.

Uncertainty surrounding the effectiveness of corticosteroids

Severe disease is characterized by diffuse lung damage, infiltration of inflammatory components, and microvascular thrombosis.

“Several therapeutic interventions to mitigate inflammatory organ injury have been proposed in viral pneumonia, but the value of corticosteroids has been widely debated,” say Horby and team.

A lack of reliable evidence from randomized clinical trials and the resulting uncertainty surrounding the effectiveness of corticosteroids has meant many COVID-19 guidelines state that these drugs are either contraindicated or not recommended.

“However, corticosteroids may modulate immune-mediated lung injury and reduce progression to respiratory failure and death,” write Horby and colleagues.

The RECOVERY trial

The authors have now described the results of dexamethasone use among hospitalized COVID-19 patients participating in the RECOVERY trial.

The study is a large randomized, controlled, open-label trial conducted across 176 NHS hospitals to compare the impact of readily available potential treatments with usual care among patients hospitalized with COVID-19.

“It has progressed at unprecedented speed, as is essential for studies during epidemics,” writes the team.

Evaluating the use of dexamethasone compared with usual care

The researchers evaluated the use of once-daily 6 mg dexamethasone for up to ten days among 2,104 patients, compared with usual care among 4,321 patients.

Participants were aged a mean of 66.1 years, and 36% were female. The primary outcome was 28-day mortality.

Overall, 454 (21.6%) of the patients who received dexamethasone died within 28 days, compared with 1,065 (24.6%) of the patients who received usual care.

Patient mortality rates varied significantly, depending on the mode of respiratory support being received at randomization.

Among patients who were receiving invasive mechanical ventilation, daily dexamethasone reduced the mortality rate by a whole third, compared with usual care (29.0% versus 40.7%). Among people who were receiving oxygen but not invasive mechanical ventilation, dexamethasone reduced mortality by one fifth (21.5% versus 25.0%).

However, dexamethasone did not significantly reduce mortality among patients who were not on any form of respiratory support.

“Clear evidence” that dexamethasone benefits patients on respiratory support

“The RECOVERY trial provides clear evidence that treatment with dexamethasone 6 mg once daily for up to 10 days reduces 28-day mortality in patients with COVID-19 who are receiving respiratory support,” say Horby and co-authors.

The teams say that based on these findings, dexamethasone would save approximately one in eight patients on invasive mechanical ventilation and around one in 25 receiving oxygen without this mechanical ventilation.

“Prior to the completion of this trial, many COVID-19 treatment guidelines have stated that corticosteroids are either ‘contraindicated’ or ‘not recommended’ in COVID-19,” write the investigators.

“These should now be updated, as has already happened within the UK. Dexamethasone provides an effective treatment for the sickest patients with COVID19 and, given its low cost, well-understood safety profile, and widespread availability, is one that can be used worldwide,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Sally Robertson

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.


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