What is the role of dexamethasone (corticosteroid) in the treatment of COVID-19 (Coronavirus disease 2019)?

From the Guidelines

Dexamethasone is recommended for hospitalized COVID-19 patients requiring supplemental oxygen or mechanical ventilation, with a standard dosage of 6 mg once daily for up to 10 days, administered orally or intravenously, as it has been shown to reduce mortality in severe cases. This recommendation is based on the most recent and highest quality study, which demonstrated a statistically significant reduction in mortality with corticosteroid treatment in patients receiving invasive mechanical ventilation and those requiring supplemental oxygen therapy 1.

Key Points

• Dexamethasone should not be used in mild cases of COVID-19 that don't require oxygen therapy, as it may be harmful in these situations.
• The anti-inflammatory effect of dexamethasone helps prevent respiratory failure and reduces mortality in severe cases by suppressing the immune system's overreaction.
• Timing is crucial, with dexamethasone being most effective when started after the first week of illness when inflammatory damage becomes predominant.
• Potential side effects include elevated blood glucose, increased risk of secondary infections, and psychiatric effects, so patients should be monitored accordingly.

Evidence Summary

The RE-COVERY trial, a multicenter RCT, found that dexamethasone reduced 28-day mortality by 35% amongst patients receiving invasive mechanical ventilation and by 20% amongst patients on supplemental oxygen therapy 1. Another study published in the European Respiratory Journal also confirmed the benefit of corticosteroids in reducing mortality in severe COVID-19 cases 1. The 2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19 also recommends the use of systemic glucocorticoids, such as dexamethasone, in patients with COVID-19 requiring supplemental oxygen or mechanical ventilation 1.

Clinical Considerations

In clinical practice, the decision to use dexamethasone in COVID-19 patients should be based on the individual patient's needs and medical history. Patients with severe COVID-19, requiring supplemental oxygen or mechanical ventilation, should be considered for dexamethasone treatment. However, patients with mild COVID-19, not requiring oxygen therapy, should not be treated with dexamethasone. Close monitoring of patients receiving dexamethasone is essential to minimize potential side effects.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Dexamethasone sodium phosphate injection has a rapid onset but short duration of action when compared with less soluble preparations. Because of this, it is suitable for the treatment of acute disorders responsive to adrenocortical steroid therapy Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, including dexamethasone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects In addition, they modify the body's immune responses to diverse stimuli. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone.

The FDA drug label does not answer the question.

From the Research

Role of Dexamethasone in COVID-19 Treatment

• Dexamethasone is a corticosteroid that has been used in the treatment of COVID-19, particularly in patients with severe or critical disease 2.
• The use of dexamethasone in COVID-19 patients has been shown to reduce 28-day mortality in those receiving invasive mechanical ventilation or oxygen alone at randomization, but not in those receiving no respiratory support 2.
• A study comparing low-dose (6 mg daily) and high-dose (20 mg daily) dexamethasone in hospitalized patients with COVID-19 pneumonia found that high-dose dexamethasone did not result in better clinical outcome improvement and was associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation 3.
• Another study compared methylprednisolone and dexamethasone in intensive care patients with COVID-19 and found that methylprednisolone was associated with lower mortality in patients requiring mechanical ventilation 4.
• A randomized controlled trial (MEDEAS) compared prolonged higher dose methylprednisolone with conventional dexamethasone in COVID-19 pneumonia and found no significant differences in 28-day mortality or mechanical ventilation-free days 5.
• The use of dexamethasone in COVID-19 patients has been shown to improve inflammatory markers, such as C-reactive protein (CRP) and ferritin, and reduce the length of stay in the intensive care unit 6.

Comparison with Methylprednisolone

• Methylprednisolone has been compared to dexamethasone in several studies, with some finding that methylprednisolone is associated with lower mortality in patients requiring mechanical ventilation 4.
• A study comparing methylprednisolone and dexamethasone in intensive care patients with COVID-19 found that methylprednisolone was associated with improved clinical outcomes, including reduced length of stay and mechanical ventilation days 6.
• However, the MEDEAS trial found no significant differences in 28-day mortality or mechanical ventilation-free days between prolonged higher dose methylprednisolone and conventional dexamethasone 5.

Dosage and Duration

• The optimal dosage and duration of dexamethasone in COVID-19 patients is still unclear, with studies using varying dosages and durations 6, 3, 2.
• The RECOVERY trial used a dose of 6 mg daily for up to 10 days, while the MEDEAS trial used a dose of 6 mg once daily for up to 10 days 2, 5.
• A study comparing low-dose and high-dose dexamethasone found that high-dose dexamethasone was associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation 3.