What medications are recommended for the treatment of COVID-19?

COVID-19 Treatment Recommendations

For non-hospitalized patients with mild COVID-19 at high risk of hospitalization, nirmatrelvir/ritonavir (Paxlovid) is the first-line treatment and should be initiated within 5 days of symptom onset. 1, 2

Treatment by Disease Severity

Non-Severe COVID-19 (High-Risk Outpatients)

Antiviral therapy should be started as soon as possible after diagnosis and within 5 days of symptom onset: 2

• Nirmatrelvir/ritonavir (Paxlovid) is the preferred option with high certainty evidence for reducing hospitalizations and mortality without increasing adverse events 1
• Molnupiravir is an alternative if nirmatrelvir/ritonavir is contraindicated due to drug interactions, though it shows less benefit than nirmatrelvir/ritonavir 1, 2
• Remdesivir (3-day course) can be considered for high-risk outpatients within 7 days of symptom onset 2, 3
• Anti-SARS-CoV-2 monoclonal antibodies should be considered if available and active against circulating variants 2

Important caveat: Nirmatrelvir/ritonavir has significant drug-drug interactions due to the ritonavir component, requiring careful medication review before prescribing 1

Corticosteroids should NOT be used in non-hospitalized patients with mild disease as they provide no benefit and may cause harm 1, 2

Moderate COVID-19 (Hospitalized, Requiring Supplemental Oxygen)

Dexamethasone 6 mg daily for 10 days is the cornerstone of therapy and strongly recommended: 1, 2

• This reduces mortality in patients requiring oxygen (high certainty evidence) 1
• Remdesivir should be added for hospitalized patients not on mechanical ventilation (5-day course, may extend to 10 days if no clinical improvement) 2, 3, 4
• Tocilizumab (IL-6 receptor blocker) should be added to dexamethasone if COVID-19-related inflammation is present, as this combination reduces disease progression and mortality 1, 2
• Baricitinib (JAK inhibitor) combined with corticosteroids can be considered, particularly for patients on high-flow oxygen or non-invasive ventilation 1

Severe/Critical COVID-19 (ICU, Mechanical Ventilation, ECMO)

Dexamethasone 6 mg daily for 10 days is strongly recommended and reduces mortality: 1, 5, 4

• Tocilizumab or sarilumab (IL-6 receptor blockers) should be added to corticosteroids for patients with elevated inflammatory markers 1, 2
• Baricitinib 4 mg daily (or renal-adjusted dose) combined with corticosteroids is recommended, with the most benefit seen in patients on high-flow oxygen/non-invasive ventilation 1
• Remdesivir may be considered for 10-day course in patients on mechanical ventilation/ECMO, though evidence is weaker in this population 3, 6, 4

Combination therapy: Baricitinib can be added to both IL-6 receptor blockers and corticosteroids based on direct trial evidence showing additional benefit 1

Supportive Care Measures

Anticoagulation

All hospitalized COVID-19 patients require thromboprophylaxis: 2, 5

• Standard prophylactic anticoagulation is recommended for all hospitalized patients 2
• Intensified prophylaxis may be indicated with additional risk factors (obesity, known thrombophilia, ICU admission, elevated D-dimers) 5

Respiratory Support

• High-flow nasal cannula (HFNC) or non-invasive CPAP is suggested for hypoxemic respiratory failure without immediate need for intubation 2, 5
• Prone positioning is recommended for patients with hypoxic respiratory failure 4

Treatments NOT Recommended

The following treatments should be avoided as they provide no benefit or cause harm:

• Hydroxychloroquine - strongly recommended against at any disease stage (increases mortality when combined with azithromycin) 1, 6, 4
• Azithromycin - should not be used without bacterial infection 1, 2, 6
• Lopinavir/ritonavir - strongly recommended against (no efficacy, high adverse event rate) 1, 2, 6, 4
• Anakinra - no robust evidence to support use 1
• Colchicine - no robust evidence at any disease stage 1
• Convalescent plasma - robust evidence against use in patients with symptom onset >5 days or who are not hypogammaglobulinemic 1, 4
• Ivermectin - insufficient evidence for recommendation 1

Special Populations

Pregnant and Breastfeeding Patients

• Nirmatrelvir/ritonavir may be considered for pregnant/breastfeeding patients with non-severe COVID-19, though data are limited 1
• Dexamethasone can be used in pregnant patients requiring oxygen 2

Immunocompromised Patients

• Pre-exposure prophylaxis with long-acting anti-SARS-CoV-2 monoclonal antibodies is recommended for unvaccinated or high-risk immunocompromised patients 2
• Post-exposure prophylaxis with monoclonal antibodies for high-risk individuals not expected to mount adequate immune response 2

Pediatric Patients

• Remdesivir dosing is weight-based for pediatric patients ≥1.5 kg (loading dose 2.5-5 mg/kg, maintenance 1.25-2.5 mg/kg depending on age and weight) 3
• Evidence for other treatments in children is limited 1

Critical Timing Considerations

Antiviral therapy must be initiated early: 1, 2, 3

• Nirmatrelvir/ritonavir and molnupiravir: within 5 days of symptom onset
• Remdesivir for outpatients: within 7 days of symptom onset
• Remdesivir for hospitalized patients: as soon as possible after diagnosis

Immunomodulatory therapy timing: 1

• Baricitinib and IL-6 receptor blockers should be initiated at the same time as corticosteroids
• No evidence supports combining multiple antiviral therapies 1

Common Pitfalls to Avoid

• Do not use corticosteroids in patients not requiring oxygen - they can be harmful in mild disease 1, 2
• Check for drug interactions before prescribing nirmatrelvir/ritonavir - ritonavir is a strong CYP3A4 inhibitor with numerous contraindicated medications 1
• Do not delay antiviral therapy - efficacy decreases significantly after 5 days of symptoms 1, 2
• Avoid hydroxychloroquine entirely - it increases cardiac complications, especially when combined with azithromycin 1, 7
• Do not use convalescent plasma routinely - only consider in immunoglobulin-deficient patients 1