What is the recommended treatment approach for a confirmed COVID‑19 patient, including severity assessment, high‑risk features, and appropriate antiviral, steroid, and immunomodulatory therapies?

COVID-19 Treatment: Evidence-Based Management Algorithm

Initial Assessment and Risk Stratification

All hospitalized COVID-19 patients should receive dexamethasone 6 mg daily for up to 10 days if they require supplemental oxygen or ventilatory support, combined with prophylactic anticoagulation. 1

Severity-Based Treatment Approach

Patients NOT requiring supplemental oxygen (SpO₂ ≥92% on room air):

• Do NOT administer corticosteroids—this increases mortality from 14.0% to 17.8% (rate ratio 1.19) 1
• Provide prophylactic-dose anticoagulation (e.g., low molecular weight heparin) 1
• Monitor oxygen saturation and respiratory rate at least twice daily, as respiratory rate elevation often precedes oxygen desaturation 1

Patients requiring supplemental oxygen:

• Initiate dexamethasone 6 mg daily (oral or IV) immediately upon oxygen requirement—this reduces mortality by 3% absolute risk reduction in low-flow oxygen patients and 35% in mechanically ventilated patients 1
• Continue for up to 10 days 1
• Target SpO₂ no higher than 96% if supplemental oxygen is necessary 1
• Continue prophylactic anticoagulation 1

Antiviral Therapy: Paxlovid (Nirmatrelvir/Ritonavir)

For non-hospitalized high-risk patients with mild-to-moderate COVID-19, prescribe Paxlovid 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days, initiated within 5 days of symptom onset. 2

High-Risk Criteria for Paxlovid:

• Age ≥65 years 2
• Immunocompromised status (hematological malignancies, transplant recipients) 2
• Unvaccinated or vaccine non-responders 2

Critical Drug Interaction Management:

• Systematically check ALL concomitant medications using the Liverpool COVID-19 Drug Interaction Tool before prescribing 2
• Ritonavir is a potent CYP3A4 inhibitor causing potentially life-threatening interactions 2
• Contraindicated with ranolazine (risk of QT prolongation and torsades de pointes) 2
• Statins (simvastatin, lovastatin) may require temporary discontinuation 2

Renal Dosing Adjustments:

• Moderate renal impairment (eGFR 30-<60 mL/min): reduce to nirmatrelvir 150 mg with ritonavir 100 mg twice daily for 5 days 2
• Severe hepatic impairment (Child-Pugh C): Paxlovid is NOT recommended 2

Special Populations:

• Pregnancy: Paxlovid may be offered to reduce disease progression; no serious adverse reactions reported in WHO Vigibase to date 2
• Age <12 years or weight <40 kg: NOT approved 2

Immunomodulatory Therapy

For patients with evidence of COVID-19-related inflammation despite corticosteroids, consider IL-6 receptor antagonist therapy (tocilizumab or sarilumab). 1

• This applies to patients requiring oxygen who show worsening despite dexamethasone 1
• Consider adding a second immunosuppressant such as IL-6 antagonist, IL-1 antagonist, or JAK inhibitor if deterioration occurs 1

Therapies to AVOID

The following interventions provide no benefit and may cause harm:

• Hydroxychloroquine: Strong recommendation AGAINST use—no clinical benefit, risk of cardiac toxicity 1
• Lopinavir-ritonavir: Strong recommendation AGAINST use—does not reduce mortality 1
• Azithromycin: Do NOT use unless documented bacterial coinfection exists 1
• Colchicine: Strong recommendation AGAINST use in hospitalized patients 1
• Interferon-β: Strong recommendation AGAINST use in hospitalized patients 1
• Routine antibiotics: Do NOT use unless clinical suspicion of bacterial infection 1

Remdesivir Considerations

Remdesivir may be considered for hospitalized COVID-19 patients, but there is no formal recommendation for non-invasively ventilated patients, and it is recommended AGAINST in invasively ventilated patients. 1

Monitoring and Common Pitfalls

Critical Monitoring Parameters:

• Oxygen saturation at least twice daily 1
• Respiratory rate at least twice daily—often the earliest sign of deterioration 1
• Work of breathing and signs of exhaustion 1

Pitfalls to Avoid:

• Do NOT delay corticosteroid therapy in patients requiring oxygen—mortality benefit is time-sensitive 1
• Do NOT give corticosteroids to non-hypoxic patients—this causes harm without benefit 1
• Do NOT delay recognition of deterioration—respiratory rate elevation precedes oxygen desaturation 1
• Do NOT delay intubation when non-invasive respiratory support fails or exhaustion appears 1
• Do NOT overlook anticoagulation in all hospitalized patients 1

Disease Pathophysiology Context

COVID-19 follows a biphasic course: an early viral replication phase (days 1-7) followed by an inflammatory lung injury phase (days 7-14+). 1

• This explains why corticosteroids benefit patients in the inflammatory phase (requiring oxygen) but harm those in the early viral phase (not requiring oxygen) 1
• Viral loads peak in the first 7 days of illness 3
• The inflammatory response involves increased IL-6, IL-8, IL-1β, D-dimer elevation, neutrophil recruitment, and T-cell activation 3