What medications and patient education are recommended for COVID-19 treatment?

COVID-19 Medications and Patient Education

For outpatients with mild COVID-19 at high risk for progression, initiate nirmatrelvir/ritonavir (Paxlovid) within 5 days of symptom onset, and for hospitalized patients requiring oxygen, immediately start dexamethasone 6 mg daily for 10 days, which is the single most important mortality-reducing intervention. 1, 2

Outpatient Treatment for Mild COVID-19

High-Risk Patients (Not Requiring Hospitalization)

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

• Nirmatrelvir/ritonavir (Paxlovid): 300 mg nirmatrelvir with 100 mg ritonavir, taken together twice daily for 5 days 3

  • Must be taken at approximately the same time each day 3
  • Can be taken with or without food 3
  • Critical drug interaction warning: Ritonavir is a strong CYP3A inhibitor that can cause severe, life-threatening interactions with many medications 3
  • Review ALL patient medications before prescribing to assess for drug-drug interactions 3

• Alternative antivirals when Paxlovid is contraindicated:

  • Remdesivir (for high-risk patients within 7 days of symptom onset) 1
  • Molnupiravir 4, 5

• Anti-SARS-CoV-2 monoclonal antibodies (if available and active against circulating variants) 1, 4

Dose Adjustments for Renal Impairment

For nirmatrelvir/ritonavir, dosing must be reduced based on kidney function: 3

• Moderate impairment (eGFR 30-59 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days
• Severe impairment (eGFR <30 mL/min): 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
• For hemodialysis patients: administer dose after dialysis 3

Symptom Management for Mild Disease

Fever management: 4

• Advise regular fluid intake (no more than 2 liters daily) 4
• Use paracetamol (acetaminophen) for fever and associated symptoms—preferred over NSAIDs until more evidence is available 4
• Do NOT use antipyretics solely to reduce body temperature 4

Cough management: 4

• Simple linctus or honey for symptomatic relief 4
• Codeine linctus, codeine phosphate tablets, or morphine sulfate oral solution only if cough is distressing 4

Critical caveat: Corticosteroids should NEVER be used in patients with mild COVID-19 who do not require oxygen—they provide no benefit and may cause harm. 1, 4

Hospitalized Patients Requiring Oxygen (Moderate COVID-19)

Core Pharmacological Treatment

Dexamethasone 6 mg daily for 10 days is mandatory—this reduces mortality and is the cornerstone of therapy: 1, 2

Remdesivir is recommended: 1, 4

• Standard dosing for hospitalized patients 4, 6
• Shown to reduce mortality risk by 54% and shorten hospital stays 7

Prophylactic anticoagulation is strongly recommended for ALL hospitalized COVID-19 patients: 2

• Low molecular weight heparin (LMWH) is preferred over unfractionated heparin due to lack of routine monitoring requirements 2

Additional Immunomodulatory Therapy

If patient is worsening despite dexamethasone AND has evidence of systemic inflammation (CRP ≥75 mg/L), add IL-6 receptor antagonist: 1, 2

• Tocilizumab or sarilumab (preferred second immunosuppressant) 1, 4
• Most beneficial when added within 24 hours of requiring noninvasive or invasive ventilatory support 2
• Reduces combined endpoint of mechanical ventilation or death (OR 0.74) 2

For seronegative patients, consider:

• Casirivimab/imdevimab (if available) 1
• High-titer convalescent plasma within 72 hours of symptom onset when monoclonal antibodies unavailable 1

Critical/Severe COVID-19 (Requiring High-Flow Oxygen, Non-Invasive or Invasive Ventilation)

Mandatory Treatments

Dexamethasone 6 mg daily is strongly recommended and should never be omitted: 1, 2

Prophylactic or therapeutic anticoagulation based on clinical assessment: 2

Add IL-6 receptor antagonist (tocilizumab or sarilumab) if COVID-19-related inflammation is present: 1, 4

• Anti-IL-1 agents (anakinra) or JAK inhibitors (baricitinib) are alternatives 4

Remdesivir Considerations

The evidence is mixed for critically ill patients: 4, 1

• WHO conditionally recommends AGAINST remdesivir in critical COVID-19, emphasizing lack of survival benefit 4
• Some guidelines suggest it may be considered for critical patients not on invasive mechanical ventilation 1
• European Respiratory Society suggests against use for patients requiring invasive mechanical ventilation 1

Respiratory Support

High-flow nasal cannula (HFNC) or noninvasive CPAP is suggested for hypoxemic respiratory failure without immediate indication for intubation: 1, 2

Special Populations

Immunocompromised Patients (Including Hematological Malignancies)

These patients face significantly higher mortality risk and require aggressive early treatment: 4

• Pre-exposure prophylaxis with long-acting anti-SARS-CoV-2 monoclonal antibodies for unvaccinated or high-risk patients 4, 1
• Post-exposure prophylaxis with monoclonal antibodies for high-risk individuals not expected to mount adequate immune response 4, 1
• Early antiviral therapy is critical 4
• Recent real-world studies support early remdesivir use in immunocompromised populations 6

Patients on Anticoagulation for Other Conditions

For patients already on anticoagulation for atrial fibrillation or other indications: 2

• Consider switching to therapeutic-dose LMWH or unfractionated heparin during hospitalization 2
• Do NOT change anticoagulant regimen based solely on D-dimer levels 2

Treatments That Should NOT Be Used

The following are strongly recommended AGAINST based on lack of efficacy or harm: 1, 2

• Hydroxychloroquine (with or without azithromycin)—no benefit, increased mortality 1, 2
• Lopinavir-ritonavir—no clinical benefit, high adverse event rate 4, 1, 2
• Azithromycin in absence of bacterial infection 2
• Corticosteroids for patients NOT requiring oxygen—no mortality benefit and potential harm 1, 2

Patient Education Essentials

When to Seek Emergency Care

Instruct patients to immediately seek medical attention if they develop: 4

• Severe breathlessness or difficulty breathing
• Persistent chest pain or pressure
• New confusion or inability to stay awake
• Blue lips or face
• Oxygen saturation <94% on room air (if home monitoring available)

Medication Adherence

For nirmatrelvir/ritonavir (Paxlovid): 3

• Complete the full 5-day course even if feeling better
• Take at the same times each day
• Inform prescriber of ALL medications, supplements, and herbal products due to serious drug interaction risk
• Common side effects include altered taste (dysgeusia) and diarrhea 3

Isolation and Transmission Prevention

Patients should isolate and avoid contact with others, especially high-risk individuals, during acute illness 4

Symptom Monitoring

Teach patients to monitor for worsening: 4

• Fever typically peaks around day 5 after exposure 4
• Breathlessness management techniques: sitting upright, leaning forward with arms braced, pursed-lip breathing 4
• Controlled breathing and relaxation techniques can help manage anxiety-related breathlessness 4

Hydration and Nutrition

Maintain adequate fluid intake (up to 2 liters daily) to prevent dehydration, especially with fever 4

Common Pitfalls to Avoid

Drug interactions with nirmatrelvir/ritonavir are the most critical safety concern—failure to review medications before prescribing can result in life-threatening events 3

Starting corticosteroids too early (in non-hypoxemic patients) causes harm without benefit—reserve dexamethasone strictly for patients requiring supplemental oxygen 1, 2

Delaying dexamethasone in hospitalized patients requiring oxygen is a missed opportunity—this is the single most important mortality-reducing intervention and should be started immediately 2

Using remdesivir in patients on invasive mechanical ventilation has questionable benefit—prioritize dexamethasone and IL-6 antagonists in this population 4, 1

Prescribing hydroxychloroquine or lopinavir-ritonavir wastes resources and may cause harm—these have been definitively shown to be ineffective 1, 2