What is the role of steroids, such as dexamethasone, in the treatment of severe Coronavirus Disease 2019 (COVID-19)?

Steroids in COVID-19: Treatment Guidelines

Dexamethasone 6 mg daily for up to 10 days is strongly recommended for patients with COVID-19 requiring supplemental oxygen, non-invasive ventilation, or mechanical ventilation, as it significantly reduces mortality in these populations. 1, 2

Evidence-Based Recommendations by Disease Severity

Mild COVID-19 (No Oxygen Requirement)

• Do not use steroids in patients who do not require supplemental oxygen
• Evidence shows no benefit and potential harm in this population (RR = 1.22) 1, 2
• Strong recommendation against steroid use in this group 1

Moderate to Severe COVID-19 (Requiring Oxygen)

• Use dexamethasone 6 mg once daily (oral or IV) for up to 10 days 1, 2
• Reduces 28-day mortality by 20% in patients on supplemental oxygen (21.5% vs. 25.0%, RR = 0.80) 2
• Consider combination with tocilizumab in rapidly deteriorating patients, as this further reduces disease progression and mortality 1

Critical COVID-19 (Requiring Mechanical Ventilation)

• Use dexamethasone 6 mg once daily (oral or IV) for up to 10 days 1, 2
• Reduces 28-day mortality by 35% in patients on invasive mechanical ventilation (29.0% vs. 40.7%, RR = 0.65) 2
• Duration should not exceed 10 days, as extended duration (>10 days) is associated with increased in-hospital mortality 3

Alternative Steroid Regimens

If dexamethasone is unavailable, methylprednisolone can be considered:

• Methylprednisolone 1-2 mg/kg/day for a short course of about 3 days 1, 2

However, caution is warranted with high-dose steroids:

• A randomized trial comparing dexamethasone 6 mg vs. 20 mg daily showed no additional benefit with higher doses 4
• Higher doses (20 mg) were associated with increased mortality in patients requiring high-flow oxygen or non-invasive ventilation 4

Mechanism of Action and Laboratory Effects

Dexamethasone works by modulating the inflammatory response in severe COVID-19:

• Reduces inflammatory markers including CRP, D-dimer, and LDH 5
• Decreases cytokine levels and endothelial markers 5
• Most effective when administered within 14 days of COVID-19 symptom onset 5

Potential Adverse Effects

Monitor for common steroid-related adverse effects:

• Hyperglycemia (blood glucose monitoring recommended)
• Hypokalemia
• Secondary infections
• Hypertension
• Delayed viral clearance

Key Clinical Pearls

1. Timing is crucial - steroids are most effective when started after the first week of symptoms when inflammatory phase predominates
2. Avoid steroids in mild cases without oxygen requirements
3. Standard dose (6 mg dexamethasone) is preferred over higher doses
4. Standard duration (10 days) is preferred over extended courses
5. Consider combination therapy with tocilizumab in rapidly deteriorating patients

The evidence clearly supports using dexamethasone in oxygen-requiring COVID-19 patients, with the strongest mortality benefit seen in those requiring mechanical ventilation. The recommended regimen remains dexamethasone 6 mg daily for up to 10 days, with no evidence supporting higher doses or extended duration.