COVID-19 Treatment
Primary Treatment Strategy
For COVID-19, treatment is stratified by disease severity: outpatients at high risk for progression should receive nirmatrelvir/ritonavir (Paxlovid) within 5 days of symptom onset; hospitalized patients requiring oxygen should receive dexamethasone 6 mg daily for up to 10 days; and those with increasing oxygen requirements plus systemic inflammation should receive the combination of dexamethasone plus tocilizumab or sarilumab. 1, 2
Outpatient Treatment (Mild-to-Moderate Disease)
High-Risk Patients Not Requiring Hospitalization
Nirmatrelvir/ritonavir (Paxlovid) is the first-line oral antiviral for adults with mild-to-moderate COVID-19 at high risk for progression to severe disease, including hospitalization or death 3
- Must be initiated within 5 days of symptom onset 3
- Dosing: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), all taken together twice daily for 5 days 3
- Critical caveat: Ritonavir is a strong CYP3A inhibitor that can cause potentially severe, life-threatening, or fatal drug interactions—review ALL patient medications before prescribing 3
- Dose adjustment required for renal impairment: patients with eGFR 30-60 mL/min receive 150 mg nirmatrelvir with 100 mg ritonavir twice daily; those with eGFR <30 mL/min receive 300 mg nirmatrelvir with 100 mg ritonavir once on day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily on days 2-5 3
Molnupiravir may be considered when nirmatrelvir/ritonavir is unavailable or contraindicated 1
Anti-SARS-CoV-2 monoclonal antibodies are recommended for high-risk patients, especially unvaccinated individuals or those with impaired immune response 1
- High-titer convalescent plasma within 72 hours of symptom onset if monoclonal antibodies are unavailable 1
Hospitalized Patients Requiring Oxygen
Corticosteroid Therapy (Foundation of Treatment)
- Dexamethasone 6 mg daily for up to 10 days or until hospital discharge is the single most important mortality-reducing intervention for hospitalized COVID-19 patients requiring supplemental oxygen, noninvasive ventilation, or mechanical ventilation 4, 1, 2
IL-6 Receptor Antagonists (Add-On Therapy)
- Tocilizumab or sarilumab should be added to corticosteroids for patients with increasing oxygen requirements AND evidence of systemic inflammation (e.g., CRP ≥75 mg/L) 4, 2
Anticoagulation
- All hospitalized COVID-19 patients should receive some form of anticoagulation 2
Respiratory Support
- High-flow nasal cannula (HFNC) or noninvasive CPAP is suggested for patients with hypoxemic acute respiratory failure without immediate indication for invasive mechanical ventilation 2
Supportive Care Measures
- Oxygen supplementation to maintain SpO2 >90-96% 1
- Careful fluid management 1
- Monitor and treat co-infections or superinfections as needed 1
Critically Ill Patients (Mechanical Ventilation)
- Continue dexamethasone 6 mg daily for up to 10 days 4, 1
- Remdesivir should NOT be used for patients requiring invasive mechanical ventilation—it may have limited benefit in this population 1, 2
- Continue prophylactic-dose anticoagulation 2
Treatments NOT Recommended
The following treatments should NOT be used for COVID-19 at any disease stage:
- Hydroxychloroquine—strongly recommended against based on large randomized trials (RECOVERY, SOLIDARITY) showing no mortality benefit and no effect on clinical outcomes 4, 2
- Azithromycin in the absence of bacterial infection 2
- Lopinavir-ritonavir 2
- Anakinra—no robust evidence to support use at any disease stage 4
- Low-dose colchicine—no robust evidence to support use at any disease stage 4
- Convalescent plasma for patients without hypogammaglobulinemia and symptom onset >5 days 4
Special Populations
Immunocompromised Patients
- Pre-exposure prophylaxis with long-acting monoclonal antibodies for unimmunized immunocompromised patients at risk for severe COVID-19 1
- Post-exposure prophylaxis with monoclonal antibodies for high-risk immunocompromised patients (unvaccinated, vaccine non-responders) 1
- Consider longer treatment duration with antivirals 1
Patients with Cardiovascular Disease
- Dual antiplatelet therapy for patients with acute coronary syndrome and COVID-19 to reduce risk of recurrent ACS or death 2
- Continue dual antiplatelet therapy for patients on DAPT receiving prophylactic-dose anticoagulant 2
- Continue antiplatelet therapy and add prophylactic-dose LMWH for patients with stroke history on antiplatelet therapy 2
Treatment Algorithm Summary
For outpatients at high risk: Nirmatrelvir/ritonavir within 5 days of symptom onset (after checking for drug interactions) 3
For hospitalized patients requiring oxygen: Dexamethasone 6 mg daily + prophylactic anticoagulation 1, 2
For hospitalized patients with increasing oxygen requirements + CRP ≥75 mg/L: Add tocilizumab or sarilumab to dexamethasone + prophylactic anticoagulation 4, 2
For critically ill patients on mechanical ventilation: Continue dexamethasone + prophylactic anticoagulation; avoid remdesivir 1, 2
Prevention Remains Critical
- COVID-19 vaccination remains the most effective means to control the pandemic and prevent severe disease 5, 6, 7
- Vaccines reduce mortality in hospitalized patients with oxygen requirements, with mRNA vaccines (BNT162b2, mRNA-1273) showing the highest effectiveness 8, 9
- Pooled vaccine effectiveness against infection is 71% after first dose and 87% after second dose; effectiveness for preventing hospitalization is 73% after first dose and 89% after second dose 9