Is it acceptable to hold off on antiviral treatment, such as oseltamivir (oseltamivir) or lopinavir/ritonavir (lopinavir/ritonavir), for patients with mild to moderate symptoms suggestive of Covid-19 (Coronavirus disease 2019) and no underlying health conditions?

Holding Off on Antiviral Treatment for Mild-Moderate COVID-19

For patients with mild to moderate COVID-19 symptoms and no high-risk features, holding off on antiviral treatment is acceptable and often recommended, as antivirals have not demonstrated clinical benefit in this population and may cause harm. 1, 2

Risk Stratification is Critical

The decision to withhold antiviral treatment depends entirely on whether the patient has high-risk features for progression to severe disease:

High-Risk Features Requiring Treatment 3, 4:

• Age ≥65 years
• Unvaccinated status
• Immunocompromised state (hematological malignancies, transplant recipients, immunosuppressive therapy)
• Multiple comorbidities
• Radiographic evidence of pneumonia

Low-Risk Patients Should NOT Receive Antivirals 3:

• The WHO explicitly recommends against treating low-risk patients with nirmatrelvir/ritonavir, as benefits are trivial and do not justify risks of drug interactions and adverse effects
• Standard supportive care is the appropriate management

Evidence Against Older Antivirals in Mild Disease

The evidence strongly argues against using repurposed antivirals like lopinavir/ritonavir, oseltamivir, or favipiravir in mild COVID-19:

Lopinavir/Ritonavir 1, 5:

• Strong recommendation AGAINST use in COVID-19 treatment
• No clear benefit beyond standard care
• Increases risk of diarrhea and nausea/vomiting

Favipiravir 2, 6:

• Associated with longer hospital stays (median 13 vs 10 days, p<0.001)
• Increased ICU admission risk (OR 3.02,95% CI 1.70-5.35)
• Increased intubation risk (OR 2.94,95% CI 1.28-6.75)

Hydroxychloroquine 1, 5:

• Strong recommendation AGAINST use
• May increase risk of death and invasive mechanical ventilation
• No benefit in viral clearance or clinical progression

Modern Antiviral Treatment: Nirmatrelvir/Ritonavir (Paxlovid)

If the patient IS high-risk, nirmatrelvir/ritonavir should be initiated within 5 days of symptom onset 3:

• Real-world effectiveness: 39% relative risk reduction in hospitalization, 61% reduction in death 3
• Dosing: 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 3
• Critical caveat: Must check for drug-drug interactions using Liverpool COVID-19 Drug Interaction Tool before prescribing 4

Supportive Care is the Standard for Mild Disease

For mild COVID-19 without high-risk features 1, 2:

• Rest and adequate nutrition/hydration
• Symptomatic treatment (antipyretics, analgesics)
• Regular monitoring for disease progression
• 97.6% of mild cases recover without complications 2

Common Pitfalls to Avoid

1. Do not prescribe antivirals "just in case" - this increases adverse events without benefit 2, 6
2. Do not delay Paxlovid beyond 5 days in high-risk patients - effectiveness drops significantly 3, 4
3. Do not use procalcitonin levels alone to guide antiviral decisions - this is for bacterial co-infection assessment 1
4. Do not prescribe Paxlovid without checking drug interactions - ritonavir is a potent CYP3A4 inhibitor with potentially life-threatening interactions 4

Algorithm for Decision-Making

1. Assess risk factors: Age, vaccination status, comorbidities, immunosuppression
2. If LOW risk: Supportive care only, no antivirals 3, 2
3. If HIGH risk AND within 5 days of symptom onset: Check drug interactions, then prescribe nirmatrelvir/ritonavir 3, 4
4. If HIGH risk BUT beyond 5 days: Consider remdesivir as alternative if hospitalized, otherwise supportive care 3