What is the role of steroids in the treatment of Covid-19?

Corticosteroid Treatment for COVID-19

For hospitalized COVID-19 patients requiring supplemental oxygen or mechanical ventilation, dexamethasone 6 mg once daily for up to 10 days should be administered, as this reduces mortality by 20-35% depending on severity of respiratory support needed. 1, 2, 3

When to Use Corticosteroids

Patients Who Should Receive Steroids

• Patients requiring supplemental oxygen: Dexamethasone reduces 28-day mortality by 20% in this population (from 26.2% to 23.3%) 1, 2
• Patients on invasive mechanical ventilation: Dexamethasone reduces mortality by 35% (from 41.4% to 29.3%) 1, 2
• Patients on non-invasive ventilation or CPAP: These patients benefit similarly to those on supplemental oxygen 1, 2

Patients Who Should NOT Receive Steroids

• Hospitalized patients NOT requiring oxygen: Corticosteroids show no mortality benefit and may actually increase mortality (14.0% vs 17.8%) 1, 2
• Outpatients with mild COVID-19: No evidence supports use and potential harm exists 3, 4
• Asymptomatic SARS-CoV-2 infection: No data supports use in this population 5, 6

Specific Dosing Recommendations

Dexamethasone (Preferred Agent)

• Standard dose: 6 mg once daily (oral or intravenous) for up to 10 days or until hospital discharge 1, 2, 3
• Do not exceed this dose: Higher doses (16 mg or 24 mg daily) worsen survival and increase adverse events compared to the standard 6-8 mg daily dose 7

Alternative Corticosteroids (If Dexamethasone Unavailable)

• Methylprednisolone: 1-2 mg/kg/day for 3-5 days (suggesting a class effect) 2, 8
• Hydrocortisone: Can be considered as alternative 8
• Prednisone: Listed as alternative option 8

The evidence suggests a class effect for corticosteroids with pooled odds ratio for mortality of 0.70 (95% CI 0.48-1.01) 1

Critical Implementation Points

Timing and Duration

• Initiate when oxygen requirement begins: Start corticosteroids as soon as supplemental oxygen is needed 3, 4
• Duration: Continue for up to 10 days or until hospital discharge, whichever comes first 1, 2, 3
• Limit duration to 3-10 days: This minimizes adverse effects while maintaining benefit 2

Combination Therapy

• With remdesivir: Consider combining dexamethasone with remdesivir (200 mg IV day 1, then 100 mg IV daily for 5-10 days) in patients requiring oxygen support 2
• With IL-6 receptor antagonists: Patients receiving tocilizumab or other IL-6 antagonists should already be on corticosteroids unless contraindicated 2
• Best candidates for additional IL-6 therapy: Those in first 24 hours after starting ventilatory support or those progressing despite corticosteroid treatment 2

Common Pitfalls and Adverse Effects

Most Common Side Effects

• Hyperglycemia: Most frequent adverse effect, especially within 36 hours of initial dose 4
• Leukocytosis: Common laboratory finding 7
• Increased infection risk: Monitor for bacterial and fungal superinfections, particularly invasive pulmonary aspergillosis in critically ill patients 1

Surgical Considerations

• Increased anastomotic leak risk: Corticosteroids impair wound healing by decreasing inflammatory cell activation and collagen synthesis 1
• Gastrointestinal complications: Risk of GI bleeding, peptic ulcer perforation, and sigmoid diverticular perforation 1
• Wound complications: Higher rates of wound infection and dehiscence 1

Special Populations

• Patients on chronic immunosuppression: Do not discontinue baseline immunosuppressants; maintain sufficient steroid dose to avoid adrenal insufficiency or disease flare 1
• Liver transplant recipients: Reduce but do not discontinue calcineurin inhibitors if pneumonia worsens; these are cornerstone medications 1
• Autoimmune liver disease: Rapid reduction risks disease exacerbation 1

Evidence Quality and Strength

The recommendation for dexamethasone is based on moderate-certainty evidence from the landmark RECOVERY trial (n=6,425 participants), which provides the strongest and most direct evidence for corticosteroid use in COVID-19 1, 2. This was a pragmatic, randomized controlled trial showing clear mortality benefit in oxygen-dependent patients. A subsequent meta-analysis of seven trials confirmed the class effect of corticosteroids with similar benefit 1, 5.

The evidence specifically demonstrates that higher doses provide no additional benefit and may cause harm 7, making the 6 mg daily dose of dexamethasone the evidence-based standard of care 1, 2, 3.