What are the treatment options for COVID-19?

Treatment for COVID-19

Treatment for COVID-19 must be stratified by disease severity and oxygen requirement, with dexamethasone 6 mg daily for 10 days as the cornerstone therapy for all hospitalized patients requiring supplemental oxygen, anticoagulation for all hospitalized patients, and antiviral therapy (nirmatrelvir/ritonavir or remdesivir) initiated within 5-7 days of symptom onset for high-risk outpatients or hospitalized patients not on mechanical ventilation. 1, 2

Treatment Algorithm by Clinical Severity

Outpatient/Mild COVID-19 (Not Requiring Oxygen)

For high-risk outpatients with mild COVID-19:

• Initiate antiviral therapy as soon as possible after diagnosis and within 5 days of symptom onset 1

  • First-line options: Nirmatrelvir/ritonavir (Paxlovid) or molnupiravir 1
  • Alternative: Anti-SARS-CoV-2 monoclonal antibodies if available and active against circulating variants 1
  • Remdesivir can be considered for high-risk patients within 7 days of symptom onset 1

• Supportive care measures: 1

  • Regular fluid intake (no more than 2 liters daily)
  • Paracetamol (acetaminophen) for fever and associated symptoms
  • Simple linctus or honey for cough; codeine or morphine only if cough is distressing

• Critical caveat: Corticosteroids should NOT be used in patients not requiring oxygen 1, 2 - this can cause harm without benefit

Hospitalized Patients NOT Requiring Oxygen

• Supportive care only 2
• Do NOT use corticosteroids - no mortality benefit and potential harm 2
• Anticoagulation recommended (prophylactic-dose) 2

Hospitalized Patients Requiring Supplemental Oxygen (Moderate COVID-19)

Core therapy (all patients in this category):

• Dexamethasone 6 mg daily for 10 days - reduces mortality by 3% 1, 2
• Prophylactic-dose anticoagulation - low molecular weight heparin (LMWH) preferred over unfractionated heparin 2
• Remdesivir 1, 3:
  • Loading dose: 200 mg IV on Day 1
  • Maintenance: 100 mg IV daily from Day 2
  • Duration: 5 days for patients not on mechanical ventilation (may extend to 10 days if no clinical improvement)
  • Must be initiated within 7 days of symptom onset

Respiratory support:

• High-flow nasal cannula (HFNC) or continuous positive airway pressure (CPAP) for hypoxemic acute respiratory failure without immediate need for intubation 2
• Maintain oxygen saturation target no higher than 96% 2

If worsening despite dexamethasone WITH evidence of systemic inflammation:

• Add IL-6 receptor antagonist (tocilizumab or sarilumab) if CRP ≥75 mg/L or other markers of inflammation present 1, 2
  • Tocilizumab: 8 mg/kg IV (not to exceed 800 mg single dose); second dose may be considered 4
  • Important caveat: The mortality benefit of tocilizumab is only demonstrated when given together with corticosteroids 4 - the effect is absent or potentially harmful without concomitant corticosteroids

For seronegative patients:

• Consider casirivimab/imdevimab or high-titer convalescent plasma within 72 hours of symptom onset if monoclonal antibodies unavailable 1

Severe/Critical COVID-19 (Requiring High-Flow Oxygen, Non-Invasive Ventilation, or Mechanical Ventilation)

Mandatory interventions:

• Dexamethasone 6 mg daily for 10 days - strongly recommended 1, 2
• Anticoagulation - all hospitalized COVID-19 patients require some form of anticoagulation 1
• Prone positioning for patients receiving invasive ventilation - reduces mortality 2

Remdesivir considerations:

• May be considered for patients not on mechanical ventilation 1, 3
• Strongly suggest AGAINST use in patients requiring invasive mechanical ventilation - no survival benefit demonstrated 2
• Duration: 10 days for patients on mechanical ventilation/ECMO (if used) 3

Immunomodulation:

• Add IL-6 receptor antagonist (tocilizumab or sarilumab) if COVID-19-related inflammation present 1, 2
• For seronegative patients on non-invasive ventilation, consider casirivimab/imdevimab 1

Critical monitoring and timing:

• Do NOT delay intubation if patients fail to respond to HFNC or CPAP within 1-2 hours 2
• Monitor renal function and platelet counts for anticoagulation decisions 2
• Do NOT change anticoagulation based solely on D-dimer levels 2

Treatments with Strong Recommendations AGAINST Use

Never use the following - no benefit and potential harm: 1, 2

• Hydroxychloroquine - strongly recommended against
• Lopinavir-ritonavir - strongly recommended against
• Azithromycin - should not be used in absence of bacterial infection

Special Populations

Immunocompromised/Hematologic Malignancies

• Pre-exposure prophylaxis: Long-acting anti-SARS-CoV-2 monoclonal antibodies for unvaccinated or high-risk patients 1
• Post-exposure prophylaxis: Anti-SARS-CoV-2 monoclonal antibodies for high-risk individuals not expected to mount adequate immune response 1
• Higher risk of severe COVID-19, particularly in those with AML, age >60 years, and active disease 1

Patients Already on Anticoagulation

• For patients on anticoagulation for conditions like atrial fibrillation, consider switching to therapeutic-dose LMWH or unfractionated heparin 1

Critical Pitfalls to Avoid

1. Do NOT use corticosteroids in patients not requiring oxygen - causes harm without benefit 1, 2

2. Do NOT use remdesivir in mechanically ventilated patients - no survival benefit 2

3. Do NOT give tocilizumab without corticosteroids - the mortality benefit requires concomitant corticosteroid therapy 4

4. Do NOT delay antiviral therapy - must be initiated within 5-7 days of symptom onset for efficacy 1, 3

5. Do NOT delay intubation in patients failing HFNC/CPAP within 1-2 hours 2

6. Ensure proper remdesivir preparation - there are TWO different formulations with different preparation methods; carefully follow product-specific instructions 3

Adjunctive Care

• Rehabilitation care should be implemented as soon as oxygenation and hemodynamics are stable 1
• Psychological support for patients experiencing anxiety, fear, or depression 1, 2
• Hepatic laboratory testing before starting and during remdesivir treatment 3
• Prothrombin time monitoring before starting and during remdesivir treatment 3

Evidence Quality Considerations

Important limitation: The mortality benefit of corticosteroids shown in open-label trials (RR 0.83) was NOT demonstrated in placebo-controlled trials (RR 0.91) when analyzed using appropriate random-effects models 4. However, given the widespread adoption and low cost, dexamethasone remains standard of care for hospitalized patients requiring oxygen.

Tocilizumab evidence concerns: The fragility index for tocilizumab mortality benefit was only 2 in REMAP-CAP, and 86% of the heterogeneity in the RECOVERY trial was attributable to concomitant corticosteroid use rather than tocilizumab itself 4. This underscores the critical importance of only using tocilizumab WITH corticosteroids.