What is the role of steroids, such as dexamethasone (corticosteroid), in treating viral infections?

Steroids in Viral Infections: A Nuanced Approach

Corticosteroids should not be routinely administered in viral infections but should be reserved for specific clinical scenarios where the benefits of controlling harmful inflammatory responses outweigh the risks of delayed viral clearance and secondary infections. 1

General Principles for Steroid Use in Viral Infections

When to Use Steroids

• Severe COVID-19 with hypoxia: Dexamethasone 6 mg daily for up to 10 days is strongly recommended for patients requiring oxygen or ventilatory support 2
• Pneumocystis Jiroveci Pneumonia with hypoxemia: Prednisolone 2×40 mg/day for 5 days, followed by 1×40 mg/day for 5 days, then 1×20 mg for 10 days 2
• Severe viral-induced ARDS: Short-term, low-dose corticosteroids may be beneficial to control overwhelming inflammation and cytokine-related lung injury 1, 3

When NOT to Use Steroids

• Mild viral infections without hypoxia: Corticosteroids may increase viral replication and delay viral clearance 2
• Early stages of viral infection: May suppress immune response needed to control viral replication 4
• Viral hepatitis and cerebral malaria: Evidence shows harm 5

Mechanism of Action in Viral Infections

Corticosteroids work through two primary mechanisms in viral infections:

1. Anti-inflammatory effects: Decrease host inflammatory responses in the lungs that may lead to acute lung injury and ARDS 1
2. Immunosuppressive effects: Inhibit activation and infiltration of inflammatory cells, macrophages, and polymorphonuclear leukocytes 1

However, these benefits come with significant risks:

• Delayed viral clearance
• Increased risk of secondary bacterial and fungal infections
• Impaired wound healing
• Metabolic complications (hyperglycemia, etc.)

Evidence from Specific Viral Infections

COVID-19

• Moderate-severe disease (requiring oxygen): Dexamethasone 6 mg daily for up to 10 days reduced 28-day mortality 1, 2
• Mild disease (no oxygen requirement): Corticosteroids NOT recommended and may be harmful 2
• Alternative regimen: Methylprednisolone 1-2 mg/kg/day for approximately 3 days may be used 1, 2

Other Coronavirus Infections (SARS, MERS)

• Historical evidence showed increased mortality, delayed viral clearance, and increased hospital stay 1
• Complications included avascular necrosis, psychosis, and diabetes 1

Influenza

• Corticosteroids increased mortality in influenza-associated ARDS 6
• Systematic review suggested increased mortality and secondary infections 1

Practical Considerations

Dosing and Duration

• Use lowest effective dose: Higher doses increase risk of complications
• Short-course therapy: Limit duration to minimize adverse effects
• Consider pulse therapy: For severe inflammation, short pulses may be more effective than prolonged courses 4

Monitoring During Therapy

• Blood glucose: Monitor for steroid-induced hyperglycemia
• Secondary infections: Vigilant monitoring, especially in patients with invasive devices 7
• Viral load: When possible, monitor for delayed viral clearance

Special Populations

• Pre-existing respiratory conditions: Continue baseline inhaled corticosteroids at usual dose for asthma/COPD, do not increase dose specifically for viral infection 2
• Immunocompromised patients: Use with extreme caution due to higher risk of secondary infections 2
• Surgical patients: Be aware of increased risk for anastomotic leakage, wound infection, and wound dehiscence 1

Common Pitfalls to Avoid

1. Initiating steroids too early in viral infection before severe inflammation develops
2. Continuing steroids too long, increasing risk of secondary infections
3. Using high doses unnecessarily, which increases adverse effects without additional benefit
4. Failing to monitor for hyperglycemia and secondary infections
5. Not considering alternative delivery methods (e.g., nebulized steroids for pulmonary inflammation) 4

In conclusion, while corticosteroids have an important role in managing severe viral infections with significant inflammatory response, their use must be carefully considered, properly timed, and appropriately dosed to maximize benefit while minimizing harm.