Risk of Post-COVID-19 Conditions Among Adolescents and Adults Who Received Nirmatrelvir-Ritonavir for Acute COVID-19: A Retrospective Cohort Study

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Background: Post-COVID-19 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: This is a 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 1 April to 31 August 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 (ie, 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: Of the treated patients, 291 433 were matched to 582 866 untreated patients. Treatment with nirmatrelvir-ritonavir reduced PCC risk in adults 50-64 years (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [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). Conclusions: 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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