What is the treatment for COVID-19, including management of symptoms and prevention of future infections?

Treatment for COVID-19

For COVID-19 treatment, initiate nirmatrelvir/ritonavir (Paxlovid) 300mg/100mg twice daily for 5 days within 5 days of symptom onset for high-risk patients with mild-to-moderate disease, combined with supportive care including oxygen supplementation to maintain SpO2 >90-96%, dexamethasone 6mg daily for up to 10 days if oxygen is required, and prophylactic anticoagulation with LMWH. 1, 2

Antiviral Therapy

First-Line Oral Antiviral

• Nirmatrelvir/ritonavir (Paxlovid) is the preferred oral antiviral for adults with mild-to-moderate COVID-19 at high risk for progression to severe disease 1, 2
• Dosing: 300mg nirmatrelvir (two 150mg tablets) with 100mg ritonavir (one 100mg tablet), all three tablets taken together twice daily for 5 days 2
• Must be initiated within 5 days of symptom onset for maximum efficacy 2
• Can be taken with or without food 2

Critical Drug Interaction Warning

• Paxlovid contains ritonavir, a strong CYP3A inhibitor that can cause potentially severe, life-threatening, or fatal drug interactions 2
• Before prescribing, review ALL patient medications to assess for interactions with CYP3A substrates 2
• Contraindicated with drugs highly dependent on CYP3A clearance (e.g., certain statins, antiarrhythmics, sedatives) 2
• Determine if concomitant medications require dose adjustment, temporary interruption, or additional monitoring 2

Dose Adjustments for Renal Impairment

• Moderate renal impairment (eGFR 30-60 mL/min): 150mg nirmatrelvir with 100mg ritonavir twice daily for 5 days 2
• Severe renal impairment (eGFR <30 mL/min) including hemodialysis:
  • Day 1: 300mg nirmatrelvir with 100mg ritonavir once
  • Days 2-5: 150mg nirmatrelvir with 100mg ritonavir once daily 2
  • Administer after hemodialysis on dialysis days 2

Alternative Antivirals

• Molnupiravir may be considered when Paxlovid is unavailable or contraindicated 1
• Remdesivir is recommended for hospitalized patients but has limited benefit in critically ill patients on mechanical ventilation 1

Corticosteroid Therapy

• Dexamethasone 6mg daily for up to 10 days is recommended for patients requiring supplemental oxygen (moderate COVID-19) 1
• Also recommended for severe/critical COVID-19 1
• Continue until hospital discharge or for maximum 10 days 1
• Do NOT use dexamethasone in mild COVID-19 patients not requiring oxygen 1

Monoclonal Antibodies

• Anti-SARS-CoV-2 monoclonal antibodies are recommended for high-risk patients with mild-to-moderate disease, 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
• Pre-exposure prophylaxis with long-acting monoclonal antibodies for unimmunized immunocompromised patients at risk for severe COVID-19 1
• Post-exposure prophylaxis for high-risk immunocompromised patients (unvaccinated or vaccine non-responders) 1
• Note: Efficacy depends on activity against the prevalent circulating variant 3

Supportive Care Measures

Oxygen Therapy

• Maintain SpO2 >90-96% with supplemental oxygen 1
• Monitor for signs of respiratory deterioration including increased work of breathing and decreasing oxygen saturation 4
• Consider escalation to high-flow oxygen, non-invasive ventilation, or mechanical ventilation based on clinical deterioration 5

Thromboprophylaxis

• Prophylactic anticoagulation with LMWH is recommended for all hospitalized COVID-19 patients 3, 1
• Adjust dosage based on renal function, weight, and bleeding risk 3
• Intensified VTE prophylaxis (intermediate or half-therapeutic LMWH dosing) should be considered in patients with:
  • BMI >30 kg/m² 3
  • History of VTE 3
  • Known thrombophilia 3
  • Active cancer 3
  • ICU admission 3
  • Rapidly increasing D-dimer levels 3

Therapeutic Anticoagulation

• In noncritically ill hospitalized patients, therapeutic-dose anticoagulation with heparin increased probability of survival compared to prophylactic dosing 3
• In critically ill patients, therapeutic anticoagulation did NOT improve outcomes compared to prophylactic dosing 3
• Use unfractionated heparin in severe renal insufficiency 3

Fluid Management and Monitoring

• Careful fluid management to avoid volume overload 1
• Monitor vital signs including heart rate, respiratory rate, and pulse oximetry 4
• Monitor for electrolyte imbalances 4

Symptom Management

• Acetaminophen for fever and pain control 4
• Appropriate analgesics for severe body aches 4
• Anti-emetics for nausea with careful QTc monitoring if combined with other medications 4

Infection Monitoring and Prevention

Bacterial Superinfection

• Close monitoring for signs of secondary bacterial infection including new fever patterns and increasing inflammatory markers 4
• Obtain blood, urine, sputum, and fecal cultures based on suspected infection site 3
• Empiric antibiotics should only be used if bacterial superinfection is suspected based on clinical deterioration and laboratory findings 3, 4
• Avoid unnecessary broad-spectrum antibiotics without evidence of bacterial infection 4

Viral Monitoring

• PCR testing on nasal, nasopharyngeal, or respiratory secretions to confirm COVID-19 diagnosis 3
• Temporarily discontinue bispecific antibody therapy in patients with COVID-19 until clinical resolution with RT-PCR clearance 3
• If asymptomatic, high cycle threshold (Ct) may indicate resolution 3
• Rapid antigen testing can confirm resolution if PCR remains persistently positive 3

Special Populations

Immunocompromised Patients

• Consider longer treatment duration with antivirals 1
• Consult infectious disease specialist if COVID-19 testing remains persistently positive 3
• Treatment should be tailored based on specific risk factors including concurrent hematological malignancies 1

Elderly Patients

• Require closer monitoring due to higher risk of complications 4
• Reduce medication doses appropriately based on organ function 4
• Use minimum effective doses for shortest duration 4
• Avoid polypharmacy 4

Vaccination

• Follow CDC or local health authority guidelines for COVID-19 vaccination 3
• Vaccinate household members and caregivers 3
• Consider two-dose series of high-dose influenza vaccine (at least one month apart) to increase likelihood of seroprotection in patients receiving immunosuppressive therapies 3

When to Escalate Care

• Worsening respiratory status with increased work of breathing or decreasing oxygen saturation 4
• Inability to maintain adequate hydration 4
• Development of new symptoms suggesting clinical deterioration 4
• Signs of secondary bacterial infection 4

Critical Pitfalls to Avoid

• Do NOT use Paxlovid without thoroughly reviewing all concomitant medications for CYP3A interactions 2
• Do NOT use dexamethasone in patients with mild COVID-19 not requiring oxygen 1
• Do NOT use therapeutic anticoagulation routinely in critically ill patients 3
• Do NOT prescribe antibiotics empirically without evidence of bacterial superinfection 3, 4
• Do NOT delay antiviral therapy—must initiate within 5 days of symptom onset 2
• Do NOT discontinue Paxlovid early—complete the full 5-day course even if symptoms improve 2