Extended antiviral therapy may not improve long COVID
Nirmatrelvir–ritonavir for up to 25 days failed to improve cognitive, autonomic, or exercise symptoms compared with placebo in a phase 2 trial.
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By
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Andrea Surnit
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September 4, 2026
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Clinical Scorecard: Extended antiviral therapy may not improve long COVID
At a Glance
| Category | Detail |
|---|
| Condition | Long COVID |
| Key Mechanisms | Nirmatrelvir–ritonavir treatment |
| Target Population | Adults aged 18 years or older with persistent symptoms for at least 12 weeks following SARS-CoV-2 infection |
| Care Setting | Randomized, double-blind, placebo-controlled trial |
Key Highlights
- Nirmatrelvir–ritonavir did not improve cognitive dysfunction, autonomic dysfunction, or exercise intolerance compared to placebo.
- The trial included 964 patients with various long COVID phenotypes.
- No statistically significant improvement was observed in primary or secondary outcomes.
- Serious adverse events occurred in 4% of patients, with no deaths reported.
- Improvement in patient-reported outcomes was noted across all treatment groups.
Guideline-Based Recommendations
Diagnosis
- Patients must have persistent symptoms for at least 12 weeks following SARS-CoV-2 infection.
Management
- Nirmatrelvir–ritonavir treatment for up to 25 days is not recommended for cognitive, autonomic, or exercise-related long COVID symptoms.
Monitoring & Follow-up
- Monitor for serious adverse events and patient-reported outcomes.
Risks
- Potential for misinterpretation of symptom improvement due to placebo effects.
Patient & Prescribing Data
Adults with long COVID symptoms for at least 12 weeks.
No significant benefit from nirmatrelvir–ritonavir treatment observed.
Clinical Best Practices
- Consider patient-reported outcomes alongside performance measures.
- Be cautious of generalizability due to demographic limitations in the study population.
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