What is the role of prednisone (40 mg orally) in the treatment of COVID-19?

Role of Prednisone 40 mg in COVID-19 Treatment

Prednisone 40 mg twice daily is not recommended for general COVID-19 treatment but may be considered in severe or critical COVID-19 patients with significant respiratory deterioration requiring oxygen support. 1

Evidence-Based Recommendations for Corticosteroid Use in COVID-19

General Recommendations:

• Corticosteroids are not recommended for patients with mild COVID-19 who do not require oxygen supplementation 1
• Corticosteroids should be used in patients requiring oxygen, non-invasive ventilation, or invasive mechanical ventilation 1, 2

Specific Guidance for Corticosteroid Selection and Dosing:

• Dexamethasone at 6 mg once daily (oral or IV) for up to 10 days is the most extensively studied corticosteroid with proven mortality benefit 1, 2
• Methylprednisolone can be considered at 1-2 mg/kg/day for a short course of about 3 days 1
• Prednisone 40 mg twice daily (as mentioned in the question) exceeds the recommended equivalent dose for most patients and should be used with caution 1

Evidence for Mortality Benefit

• The RECOVERY trial (n=6425) demonstrated that dexamethasone reduced 28-day mortality by:

  • 35% in patients on invasive mechanical ventilation (29.0% vs. 40.7%, RR=0.65) 1, 2
  • 20% in patients on supplemental oxygen (21.5% vs. 25.0%, RR=0.80) 1, 2
  • No benefit was observed in mild cases not requiring oxygen (17.0% vs. 13.2%, RR=1.22) 1, 2

• A systematic review including multiple corticosteroids suggests a class effect with an overall odds ratio for mortality of 0.70 (95% CI 0.48-1.01) 1, 3

Important Considerations and Cautions

• Timing is critical: Corticosteroids should be initiated when patients develop significant respiratory symptoms requiring oxygen 1
• Duration should be limited: Short courses (3-10 days) are recommended to minimize adverse effects 1
• Potential harms in mild disease: Corticosteroids may worsen outcomes in patients not requiring oxygen by suppressing immune response and increasing risk of secondary infections 1, 4
• Monitoring required: Watch for hyperglycemia, secondary infections, and other steroid-related complications 4

Special Situations

• COVID-19 with myocarditis: Corticosteroids may be beneficial in patients with COVID-19-associated myocarditis, particularly with hemodynamic compromise 1
• Severe inflammatory response: Higher doses may be considered in patients with evidence of cytokine storm or MIS-A (multisystem inflammatory syndrome in adults) 1

Alternative Corticosteroid Regimens

• One study comparing high-dose methylprednisolone (250-500 mg daily for 3 days) to dexamethasone 6 mg showed potential benefits with methylprednisolone including:
  • Shorter recovery time (3 days vs 6 days) 5
  • Lower ICU transfer rates (4.8% vs 14.4%) 5
  • Lower mortality (9.5% vs 17.1%) 5
  • However, this requires confirmation in larger randomized trials

Conclusion

For the specific question about prednisone 40 mg twice daily for COVID-19, the evidence does not support this particular regimen for general use. If corticosteroids are indicated (in patients requiring oxygen), dexamethasone 6 mg daily is the best-supported option, with methylprednisolone as an alternative at 1-2 mg/kg/day for a short course. Prednisone could be used as an alternative when dexamethasone is unavailable, but the dose should be equivalent to dexamethasone 6 mg (approximately prednisone 40 mg once daily, not twice daily).