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RECOVERY – Dexamethasone for COVID-19

August 20, 2020

Written by Sam Parnell

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The use of dexamethasone was associated with lower mortality for patients hospitalized with COVID-19 receiving invasive mechanical ventilation or supplemental oxygen therapy. There was no benefit for patients who did not require initial respiratory support.

Why does this matter?
COVID-19 has been running rampant across the world, sickening millions, killing hundreds of thousands, shutting down economies, and drastically changing our way of life. Most patients infected with the SARS-CoV-2 virus are asymptomatic or have mild disease. However, a significant number of individuals develop severe infections that can lead to respiratory failure and death. Several therapeutic options have been investigated, but there has been little evidence that any of them actually reduce mortality. We have been desperate for a glimmer of hope that a treatment modality (besides good supportive care) can help turn the tide on this global pandemic. Researchers believe that immune response may play an important role in the pathophysiology of severe COVID-19. Could glucocorticoids decrease this inflammatory response, reduce mortality, and provide a much-needed tool in our fight against COVID-19?

Improved RECOVERY with Dexamethasone for Severe COVID-19
The RECOVERY trial was a controlled, open-label, pragmatic trial of 6,425 patients hospitalized with COVID-19 comparing 28-day mortality for patients randomly assigned to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days versus usual care alone.

Overall, patients receiving dexamethasone had lower incidence of death compared to usual care (22.9% vs. 25.7%; rate ratio, 0.83; 95% CI, 0.75 to 0.93). The greatest benefit was seen with the sickest patients and those with a longer duration of symptoms. Specifically, there was a significant reduction in mortality for patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94). Patients with no respiratory support at randomization did not have a statistically significant benefit from dexamethasone therapy (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55), and there was even a signal of possible harm, perhaps due to patients being in the early viral replication stage of the disease instead of the later host inflammatory stage. 

For secondary outcomes, patients in the dexamethasone group also had shorter duration of hospitalization (median, 12 days vs. 13 days), higher probability of discharge alive within 28 days (rate ratio, 1.10; 95% CI, 1.03 to 1.17), and lower risk of progression to mechanical ventilation (risk ratio, 0.77; 95% CI, 0.62 to 0.95).

Rarely do I immediately change my clinical practice based on a single study, and I would love to see these results validated in a large, blinded, randomized controlled trial.  However, based on these promising results, the fact that dexamethasone is inexpensive and widely available, and with few other evidence-based therapeutic options available to treat patients with COVID-19, I plan to administer dexamethasone to any patient with COVID-19 who requires oxygen or ventilatory support.

Source
Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020 Jul 17. doi: 10.1056/NEJMoa2021436. [Epub ahead of print]

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