What is the recommended treatment for COVID-19 (Coronavirus disease 2019)?

Treatment of COVID-19

For mild-to-moderate COVID-19 in adults at high risk for progression to severe disease, initiate Paxlovid (nirmatrelvir/ritonavir) as soon as possible after diagnosis and within 5 days of symptom onset. 1

Antiviral Therapy

Primary Antiviral Treatment

• Paxlovid (nirmatrelvir 300 mg with ritonavir 100 mg) taken orally twice daily for 5 days is the FDA-approved treatment for mild-to-moderate COVID-19 in high-risk adults 1
• Treatment must be initiated within 5 days of symptom onset for maximal efficacy 1
• Dose adjustment required for moderate renal impairment (eGFR 30-60 mL/min): reduce to nirmatrelvir 150 mg with ritonavir 100 mg twice daily 1
• Not recommended in severe renal impairment (eGFR <30 mL/min) or severe hepatic impairment 1

Critical Warning: Paxlovid contains ritonavir, a strong CYP3A inhibitor that causes potentially severe drug-drug interactions. Review all patient medications before prescribing and assess whether concomitant drugs require dose adjustment, interruption, or additional monitoring 1

Alternative Antiviral Options

For patients with mild COVID-19 when Paxlovid is contraindicated or unavailable 2:

• Remdesivir (intravenous administration) 2
• Molnupiravir (oral) 2
• Inhaled interferon β-1a 2

Severity-Based Treatment Algorithm

Mild COVID-19 (No Respiratory Distress, SpO2 >94%)

• Antiviral therapy with Paxlovid if high-risk patient 1
• Monoclonal antibodies (if available and effective against circulating variant) 2
• Do NOT use dexamethasone in mild disease 2
• Supportive care with adequate nutrition and hydration 3
• Monitor vital signs, blood routine, organ function, and chest imaging regularly 3

Moderate COVID-19 (Oxygen Support Needed, SpO2 >90%)

The following combination is recommended 2, 3:

• Remdesivir 2
• Dexamethasone (methylprednisolone 40-80 mg daily, not exceeding 2 mg/kg/day for 3-5 days) 2, 3
• If patient is seronegative for SARS-CoV-2 antibodies, add casirivimab/imdevimab or convalescent plasma 2
• If worsening despite dexamethasone with ongoing COVID-19-related inflammation, add second immunosuppressant: tocilizumab, sarilumab, anakinra, or baricitinib/tofacitinib 2

Severe COVID-19 (SpO2 <94%, RR >30/min, or lung infiltrates >50%)

Treatment includes 2, 3:

• Dexamethasone (strong recommendation) 2
• Remdesivir 2
• If seronegative and on non-invasive ventilation, consider casirivimab/imdevimab 2
• Add second immunosuppressant (tocilizumab or sarilumab) if COVID-19-related inflammation persists 2
• Effective oxygen therapy: high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), or invasive mechanical ventilation based on severity 3

Critical COVID-19 (ARDS, Septic Shock, Mechanical Ventilation)

• Dexamethasone (high-certainty evidence for mortality benefit) 2
• Remdesivir 2
• Anti-IL-6 therapy (tocilizumab or sarilumab) for COVID-19-related inflammation 2
• Consider ECMO for refractory hypoxemia unresponsive to protective lung ventilation 3
• For septic shock: early recognition with norepinephrine as first-choice vasopressor after fluid resuscitation 3

Antibiotic Considerations

Do NOT routinely prescribe antibiotics to every COVID-19 patient 2

When to Consider Antibiotics

Antibiotics should only be used based on clinical justifications 2:

• Critically ill patients (ICU admission or mechanical ventilation) have higher risk of bacterial coinfection 2
• Higher WBC counts, elevated CRP, or procalcitonin >0.5 ng/mL suggest possible bacterial infection, but do not use biomarkers alone to initiate antibiotics in non-critically ill patients 2
• Do NOT routinely give antibiotics to patients receiving corticosteroids or IL-6 inhibitors 2

Antibiotic Selection When Indicated

For bacterial coinfection (non-ICU) 2:

• Cover typical and atypical community-acquired pneumonia pathogens (amoxicillin, azithromycin, or fluoroquinolones) 2, 3
• Duration: 7 days if afebrile for 48 hours and clinically stable 2

For bacterial coinfection (ICU/critically ill) 2:

• Add empirical anti-MRSA coverage in selected patients 2

For secondary bacterial infection (non-ICU) 2:

• Single antipseudomonal antibiotic 2

For secondary bacterial infection (ICU/critically ill) 2:

• Double antipseudomonal and/or anti-MRSA antibiotics based on local epidemiology 2

Always obtain comprehensive microbiologic workup before starting empirical antibiotics to facilitate de-escalation or discontinuation 2

Supportive Care Essentials

Nutritional Support

• Protein-rich foods with energy intake of 25-30 kcal/(kg·d) and protein 1.5 g/(kg·d) for patients with nutrition risk scores <3 3
• For nutrition risk scores ≥3: increase protein through oral supplements 2-3 times daily (≥18g protein/time) 3

Thromboprophylaxis

• Evaluate venous thromboembolism risk and use low-molecular-weight heparin or heparin in high-risk patients without contraindications 3

Gastrointestinal Protection

• Use H2 receptor antagonists or proton pump inhibitors in patients with gastrointestinal bleeding risk factors 3

Respiratory Secretion Management

• For dyspnea, cough, wheeze, and respiratory distress due to increased secretions: selective M1/M3 receptor anticholinergic drugs to reduce secretion and improve pulmonary ventilation 3

Vaccination

All persons aged ≥6 months should receive updated COVID-19 vaccines 4

• Updated 2023-2024 formula vaccines (monovalent XBB.1.5 component) are recommended to provide protection against currently circulating variants 4
• Adults aged ≥65 years and immunocompromised individuals should receive booster doses for maximal protection 5
• Vaccination significantly reduces hospitalization and death from COVID-19 6

Discharge Criteria

Patients may be discharged when ALL of the following are met 3:

• Body temperature normal for more than 3 days 3
• Respiratory symptoms significantly improved 3
• Lung inflammation showing obvious absorption on imaging 3
• Two consecutive negative respiratory nucleic acid tests (one-day sampling interval) 3

Common Pitfalls to Avoid

• Do not delay Paxlovid initiation - must start within 5 days of symptom onset 1
• Do not overlook drug interactions with Paxlovid - ritonavir causes significant CYP3A interactions that can be life-threatening 1
• Do not use corticosteroids in mild COVID-19 - they provide no benefit and may cause harm 2
• Do not prescribe antibiotics empirically without clinical justification - this drives antimicrobial resistance 2
• Do not use biomarkers alone to decide antibiotic initiation in non-critically ill patients 2