A 42-year-old woman with no comorbidities presents with a 3-day history of fever, sore throat, and mild cough. RT-PCR confirms SARS-CoV-2 infection. She is fully vaccinated. SpO₂ is 96% on room air, and she has no respiratory distress. She is at high risk for severe disease due to recent chemotherapy for breast cancer. What is the drug of choice for early treatment?

Explanation

## Antiviral Choice in Mild-to-Moderate COVID-19 with High-Risk Features **Key Point:** Paxlovid (nirmatrelvir/ritonavir) is the preferred oral protease inhibitor for mild-to-moderate COVID-19 in high-risk patients when started within 5 days of symptom onset. It has the strongest evidence for reducing hospitalization and mortality in this population. ### Clinical Context This patient has: - **Mild disease** (SpO₂ 96%, no respiratory distress) - **High-risk feature** (recent chemotherapy → immunocompromised) - **Early presentation** (day 3 of illness → within treatment window) - **No contraindications** to protease inhibitors ### Comparison of Oral Antivirals for Mild-to-Moderate COVID-19 | Feature | Paxlovid | Molnupiravir | Favipiravir | |---------|----------|-------------|-------------| | **Drug class** | Protease inhibitor (3CL protease) | Nucleoside analog (mutagenic) | RdRp inhibitor | | **Efficacy (hospitalization reduction)** | 89% (EPIC-HR trial) | 30% (MOVe-OUT trial) | ~60% (variable data) | | **Dosing** | Oral, 5 days | Oral, 5 days | Oral, 5 days | | **Timing** | Within 5 days of symptom onset | Within 5 days of symptom onset | Within 5 days of symptom onset | | **Drug interactions** | Significant (CYP3A4 inhibitor + ritonavir) | Minimal | Minimal | | **Pregnancy** | Compatible (Category B equivalent) | Contraindicated (teratogenic) | Contraindicated (teratogenic) | | **Immunocompromised patients** | Preferred (strongest evidence) | Alternative | Alternative | | **Renal impairment** | eGFR ≥30 (standard); <30 (dose adjust) | eGFR ≥30 (standard) | No dose adjustment needed | **High-Yield:** Paxlovid demonstrated an **89% reduction in hospitalization/death** in the EPIC-HR trial (high-risk patients with mild-to-moderate disease). This is the strongest efficacy signal among oral antivirals and makes it the preferred choice for this patient. ### Why Paxlovid Is First-Line Here 1. **Highest efficacy** in mild-to-moderate disease with risk factors (89% vs. 30% for molnupiravir) 2. **Immunocompromised host** → protease inhibitor preferred 3. **Early presentation** (day 3) → optimal timing for oral therapy 4. **No contraindications** (no severe renal impairment, no major drug interactions listed) **Clinical Pearl:** Paxlovid consists of nirmatrelvir (3CL protease inhibitor) + ritonavir (CYP3A4 inhibitor to boost nirmatrelvir levels). Standard dose: 2 tablets (nirmatrelvir 150 mg + ritonavir 100 mg) twice daily for 5 days. Must be started within 5 days of symptom onset. **Warning:** Paxlovid has significant drug interactions (CYP3A4 inhibition). Check for interactions with chemotherapy agents, cardiac drugs, and anticoagulants. Ritonavir can transiently elevate liver enzymes and lipids.