What is the recommended treatment for COVID-19?

Treatment for COVID-19

The recommended treatment for COVID-19 is stratified by disease severity: supportive care for all patients, remdesivir for hospitalized patients, dexamethasone 6 mg daily for those requiring oxygen, and nirmatrelvir/ritonavir or monoclonal antibodies for high-risk outpatients within 7 days of symptom onset. 1, 2, 3

Disease Severity Classification

Before initiating treatment, classify patients into severity categories 2:

• Mild illness: Symptoms present without respiratory distress or abnormal imaging 2
• Moderate illness: Lower respiratory disease with SpO2 ≥94% on room air 2
• Severe illness: SpO2 <94% on room air, PaO2/FiO2 <300 mmHg, respiratory rate >30 breaths/min, or lung infiltrates >50% 2
• Critical illness: Requires ICU admission, mechanical ventilation, or presents with septic shock 2

Outpatient Management (Mild-to-Moderate Disease)

High-Risk Patients

Treatment must be initiated within 7 days of symptom onset 2:

• First-line: Nirmatrelvir/ritonavir (oral antiviral) 1, 2
• Alternative: Anti-SARS-CoV-2 monoclonal antibodies, particularly for unvaccinated individuals or those with impaired immune response 1, 2
• Second alternative: Molnupiravir when other options are unavailable 1, 2

Low-Risk Patients

• Home isolation with supportive care 2
• Monitor for progression to severe disease 2

Critical pitfall to avoid: Do not delay treatment initiation in high-risk patients—begin as soon as possible after diagnosis 2

Hospitalized Patients (Not Requiring Oxygen)

• Do NOT use corticosteroids in hospitalized patients not requiring supplemental oxygen or ventilatory support 4
• Provide supportive care with careful fluid management 1
• Implement thromboprophylaxis with anticoagulation 1, 2

Hospitalized Patients Requiring Oxygen

Corticosteroid Therapy

Dexamethasone 6 mg daily for up to 10 days or until hospital discharge 4, 1, 2:

• This applies to patients requiring oxygen, noninvasive ventilation, or invasive mechanical ventilation 4
• The RECOVERY trial demonstrated significant mortality reduction in patients receiving invasive mechanical ventilation (41.4% vs 29.3%) and those requiring supplemental oxygen (26.2% vs 23.3%) 4

Antiviral Therapy

Remdesivir 2, 3:

• Adults and pediatric patients ≥40 kg: Loading dose of 200 mg on Day 1, followed by 100 mg daily from Day 2 3
• Treatment duration: 5 days for non-ICU patients not requiring mechanical ventilation 2, 3
• If no clinical improvement after 5 days, extend for up to 5 additional days (total 10 days) 3
• Administer via IV infusion over 30-120 minutes 3

Supportive Measures

• Oxygen supplementation to maintain SpO2 >90-96% 1
• Thromboprophylaxis with anticoagulation (continue pre-existing antiplatelet therapy and add prophylactic-dose LMWH) 2
• Monitor for co-infections or superinfections 1

ICU/Critically Ill Patients

Mechanical Ventilation and ECMO

Remdesivir 10-day course for patients requiring invasive mechanical ventilation and/or ECMO 2, 3:

• Loading dose of 200 mg on Day 1, followed by 100 mg daily 3
• Note: Remdesivir may have limited benefit in critically ill patients on mechanical ventilation 1

Corticosteroids

Dexamethasone 6 mg daily for up to 10 days 4, 1, 2

Additional Therapies

• Consider IL-6 inhibitors when condition deteriorates dramatically 2
• Early endotracheal intubation if oxygenation index <150 mmHg within 1-2 hours 2
• High-flow nasal cannula (HFNC) or noninvasive CPAP via helmet or facemask for hypoxemic acute respiratory failure without immediate indication for invasive mechanical ventilation 4

Antibiotic Considerations

Avoid routine prescription of antibiotics unless bacterial infection is clinically suspected 2:

• Base antibiotic decisions on clinical justification, disease manifestations, severity, imaging, and laboratory data 2
• Perform comprehensive microbiologic workup before administering empirical antibiotics 2
• Few COVID-19 patients have secondary bacterial infections, and antibiotic misuse leads to higher resistance rates 4

Monitoring Requirements

Hepatic Function

• Perform hepatic laboratory testing before starting remdesivir and during treatment as clinically appropriate 3
• Consider discontinuing remdesivir if ALT >10 times upper limit of normal 3
• Discontinue remdesivir if ALT elevation is accompanied by signs or symptoms of liver inflammation 3

Coagulation

• Assess prothrombin time before starting remdesivir and monitor as clinically appropriate 3

Hypersensitivity

• Monitor patients during remdesivir infusion and observe for at least one hour after completion 3
• Slower infusion rates (up to 120 minutes) can prevent hypersensitivity reactions 3

Special Populations

Immunocompromised Patients

• Pre-exposure prophylaxis with long-acting monoclonal antibodies for unimmunized patients at risk for severe COVID-19 1
• Post-exposure prophylaxis with monoclonal antibodies for high-risk patients (unvaccinated, vaccine non-responders) 1
• Consider longer treatment duration with antivirals 1

Renal Impairment

• No dosage adjustment of remdesivir required for any degree of renal impairment, including dialysis 3

Therapies NOT Recommended

Strong recommendations against 4:

• Hydroxychloroquine (strong recommendation against use) 4
• Azithromycin in absence of bacterial infection 4
• Hydroxychloroquine and azithromycin combination 4
• Lopinavir-ritonavir 4
• Colchicine 4
• Interferon-β 4

Important caveat: Coadministration of remdesivir with chloroquine phosphate or hydroxychloroquine sulfate is not recommended due to potential antagonistic effects on remdesivir's antiviral activity 3

Discharge Criteria

Patients may be discharged when 2:

• Temperature returned to normal for >3 days 2
• Significant improvement in respiratory symptoms 2
• Significant absorption of pulmonary lesions on CT imaging 2

Post-Discharge Management

• Home quarantine for 2 weeks after discharge 2
• PCR tests at 2 and 4 weeks post-discharge 2
• Patients retesting positive should be isolated again 2

Common Pitfalls to Avoid

• Do not delay treatment in high-risk outpatients—initiate within 7 days of symptom onset 2
• Do not use corticosteroids in hospitalized patients not requiring oxygen 4
• Do not use multiple antiviral drugs simultaneously 2
• Do not neglect thromboprophylaxis in hospitalized patients 1, 2
• Do not fail to monitor for drug interactions, especially with anticoagulants and antiplatelet agents 2
• Do not use antibiotics routinely without clinical justification for bacterial infection 2