What is the recommended treatment for a patient with severe COVID-19 (Coronavirus Disease 2019)?

Treatment of Severe COVID-19

For severe COVID-19, immediately initiate dexamethasone 6 mg daily for 10 days combined with baricitinib 4 mg daily, provide aggressive respiratory support with oxygen therapy or non-invasive ventilation, and add tocilizumab for patients with CRP ≥100 mg/L or elevated IL-6. 1, 2

First-Line Pharmacologic Treatment

Corticosteroids (Mandatory)

• Administer dexamethasone 6 mg daily for 10 days to all patients with severe COVID-19 requiring oxygen therapy, non-invasive ventilation, or invasive mechanical ventilation 3, 1, 4
• This reduces all-cause mortality by 3%, decreases mechanical ventilation requirements, and improves disease progression with moderate certainty evidence 3, 1
• The mortality benefit is most pronounced in patients on invasive mechanical ventilation (41.4% vs 29.3%) and those requiring supplementary oxygen (26.2% vs 23.3%) 3
• Critical error: Do NOT use corticosteroids in patients not requiring supplemental oxygen, as this provides no benefit and may worsen outcomes 3, 4, 5
• Monitor for hyperglycemia as the primary adverse effect 3

Immunomodulatory Therapy

• Add baricitinib 4 mg daily for up to 14 days or until hospital discharge to corticosteroids, demonstrating the most benefit in patients with severe COVID-19 on high-flow oxygen/non-invasive ventilation at baseline 1
• For patients with CRP ≥100 mg/L or elevated IL-6 who are on oxygen support, administer tocilizumab or sarilumab 3, 1, 2
• Tocilizumab reduces all-cause mortality and 14-day requirements for non-invasive and invasive mechanical ventilation, with greater mortality reduction at higher CRP levels (≥100 mg/L) 3
• The FDA specifically indicates tocilizumab for hospitalized COVID-19 patients receiving systemic corticosteroids who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO 2

Antiviral Therapy (Limited Role)

• For patients receiving oxygen therapy but NOT on invasive mechanical ventilation, consider remdesivir 200 mg loading dose on Day 1, then 100 mg daily for 5 days (weak recommendation, moderate evidence quality) 3, 1
• The FDA recommends a 10-day course for patients requiring invasive mechanical ventilation/ECMO, but guidelines suggest NOT using remdesivir in mechanically ventilated patients 3, 1, 6
• Treatment should be initiated as soon as possible after diagnosis 6

Immunoglobulin Therapy

• For patients who fail to respond to initial therapy, consider intravenous immunoglobulin (IVIg) (strong recommendation, moderate evidence quality) 3

Respiratory Support Strategy

Oxygen Therapy Algorithm

• Immediately provide oxygen therapy to maintain SpO2 92-96% in patients without chronic lung disease 3, 7
• For patients with PaO2/FiO2 <300 mmHg, immediately initiate adjuvant oxygen therapy and airway management 3
• If respiratory distress or hypoxemia does not improve within 1-2 hours of nasal catheter or mask oxygen, escalate to high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV) 3
• If condition does not improve after 1-2 hours of HFNC/NIV, perform invasive mechanical ventilation (IMV) immediately 3
• Consider extracorporeal membrane oxygenation (ECMO) if available for refractory cases 3

Awake Prone Positioning

• For patients receiving HFNC or NIV, implement concurrent awake prone ventilation for >12 hours daily if no contraindications exist (weak recommendation, low evidence quality) 3

Critical Monitoring Requirements

Close Clinical Surveillance

• Monitor continuously for signs of clinical deterioration including rapid progressive respiratory failure and shock 3
• Evaluate respiratory rate, oxygen saturation, and work of breathing every 1-2 hours during initial stabilization 3
• Aggressively monitor for secondary bacterial infections, as severe COVID-19 patients demonstrate significantly higher infection susceptibility 3, 1, 4

Laboratory Monitoring

• Closely monitor D-dimer levels and coagulation parameters given increased thromboembolic risk 3, 4
• For patients with suspected or confirmed myocardial injury, repeat high-sensitivity troponin measurements daily with continuous ECG monitoring 3
• Monitor blood pressure, heart rate, and fluid balance closely 3
• Perform hepatic laboratory testing before starting and during treatment with remdesivir 6
• Determine prothrombin time before starting remdesivir and monitor as clinically appropriate 6

Thromboembolism Surveillance

• Implement anticoagulation therapy for all hospitalized patients with severe COVID-19 (strong recommendation, very low evidence quality) 3
• Actively monitor for signs of thromboembolism including stroke, deep vein thrombosis, pulmonary embolism, or acute coronary syndrome 3
• If clinically suspected, initiate appropriate diagnostic and management pathway immediately 3

Treatments to AVOID

Hydroxychloroquine

• Do NOT use hydroxychloroquine, as it increases risk of death and invasive mechanical ventilation without improving viral clearance, clinical progression, or length of hospital stay 3, 1, 4, 5
• It may increase adverse effects including diarrhea and nausea/vomiting 3

Lopinavir/Ritonavir

• Do NOT use lopinavir/ritonavir, as it provides no benefit and increases risk of diarrhea and nausea/vomiting 3, 1, 4, 5

Other Agents

• Do NOT use azithromycin in the absence of bacterial infection (conditional recommendation, very low evidence) 3
• Do NOT use colchicine for hospitalized patients (conditional recommendation, very low evidence) 3
• Do NOT use interferon-β (conditional recommendation, very low evidence) 3

Supportive Care Measures

Complication Management

• Actively manage complications including treatment of underlying diseases and prevention of secondary infections 3
• Provide timely support of organ function 3
• Evaluate all patients for risk of hemorrhage immediately after admission 3

Drug-Drug Interactions

• Use medications with the lowest risk of drug-drug interactions; for dose-dependent medications, use minimum effective doses for the shortest duration 3
• Consider both pharmacokinetic and pharmacodynamic effects when selecting therapies 3

Special Considerations for Elderly Patients

• Reduce all COVID-19 medications to 1/2 of standard adult doses for patients over 80 years old due to deteriorated liver and kidney function 4
• Review all current prescriptions to minimize polypharmacy and prevent dangerous drug-drug interactions 4
• Ensure adequate nutritional support with protein-rich foods: ideal energy intake of 25-30 kcal/(kg·day) and protein intake of 1.5 g/(kg·day) 5
• Engage multidisciplinary team including community workers, nurses, pharmacists, physiotherapists, and mental health providers 4

Common Pitfalls to Avoid

• Using corticosteroids too early (before oxygen requirement develops) worsens outcomes and delays viral clearance 1, 4
• Continuing remdesivir in patients on mechanical ventilation provides no benefit 1
• Failing to add baricitinib to corticosteroids misses the synergistic benefit demonstrated in severe disease 1
• Not monitoring for secondary infections in elderly patients who have significantly higher infection susceptibility 1, 4
• Using treatment with >5 L oxygen/min without close collaboration with intensive care colleagues 7
• Administering nebulized medications instead of using spacers, which increases aerosolization risk 7