Publication date: May 30, 2025

Introduction: Post-COVID Conditions (PCC) potentially affect millions of people, but it is unclear whether treating acute COVID-19 with nirmatrelvir-ritonavir may reduce the risk of PCC. Methods: Retrospective cohort study using real-world, closed claims data to assess the relationship between nirmatrelvir-ritonavir and PCC by age group (12-17, 18-49, 50-64, [≥]65 years). Eligible patients had a COVID-19 index date (positive laboratory test, ICD-10 diagnosis code, or nirmatrelvir-ritonavir prescription) from April 1 – August 31, 2022, in the outpatient, telehealth, or emergency department setting, and had a higher risk of severe COVID-19 based on age ([≥]50 years) or underlying risk factors. Treated patients (i.e., received a nirmatrelvir-ritonavir prescription within +/- 5 days of index date) were matched 1:2 on age, sex, month of index date, and HHS region with untreated patients. PCC was defined by the presence of [≥]1 of 45 new-onset symptoms or conditions recorded [≥]60 days after index date. Results: 291,433 treated patients were matched to 582,866 untreated patients. Treatment with nirmatrelvir-ritonavir reduced PCC risk in adults 50-64 years (aHR 0.93, 95%CI 0.92-0.95) and [≥]65 years (aHR 0.88, 95% CI 0.87-0.90). Treatment had minimal effect among high-risk adults 18-49 years (aHR 0.98, 95% CI 0.97-0.99), and no effect among high-risk adolescents 12-17 years (aHR 1.06, 95% CI 0.66-1.13). Conclusion: Results using real-world data suggest a protective relationship between nirmatrelvir-ritonavir during acute illness and PCC risk among older adults, but not among adolescents. Consideration may be given to outpatient treatment of mild to moderate COVID-19 with nirmatrelvir-ritonavir to reduce the risk of severe disease and PCC.

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