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Peer-reviewedCC BYPLOS Global Public Health

Real-world effectiveness of Paxlovid in protecting Long COVID for outpatient adult patients: A target trial emulation study from the RECOVER Initiative

  • Fei Wang1,2,3,4,5,6,7,8,9
  • Haoyang Li1
  • Dhruv Khullar1,2,3,4,5,6,7,8,9
  • Yongkang Zhang1,2,3,4,5,6,7,8,9
  • Stephenson Strobel1
  • Yong Chen10,2,3,4,5,6,7,8,1,9
  • Marc A. Sala11,2,3,4,5,6,7,8,1,9
  • Payal B. Patel12,2,3,4,5,6,7,8,1,9
  • Alejandro P. Comellas7,2,3,4,5,6,8,1,9
  • Andrew Wylam13,2,3,4,5,6,7,8,1,9
  • Mark Weiner1,14,2,3,4,6,7,8,9
  • Chris B. Forrest15,2,3,4,5,6,7,8,1,9
3 more authors
  • Thomas W. Carton16,2,3,4,5,6,7,8,1,9
  • Fei Wang1,2,3,4,5,6,7,8,9
  • Rainu Kaushal1,17
17 affiliations
  1. 1Weill Cornell Medicine
  2. 2Children's Hospital of Philadelphia
  3. 3Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania
  4. 4Louisiana Public Health Institute Rainu Kaushal Weill Cornell Medicine, New York, NY
  5. 5National Institutes of Health's RECOVER Initiative
  6. 6Northwestern University
  7. 7University of Iowa
  8. 8University of Washington School of Medicin
  9. 9Weill Cornell Medicine Yongkang Zhang Weill Cornell Medicine
  10. 10University of Pennsylvania Perelman School of Medicine
  11. 11Northwestern University Feinberg School of Medicine
  12. 12University of Washington School of Medicine
  13. 13Patient representative for Long COVID patients with the National Institutes of Health’s RECOVER Initiative
  14. 146Patient representative for Long COVID patients with the National Institutes of Health’s RECOVER Initiative
  15. 15Applied Clinical Research Center, Children’s Hospital of Philadelphia
  16. 16Louisiana Public Health Institute
  17. 17Weill Cornell Medicine, New York, NY
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Abstract

Paxlovid (nirmatrelvir/ritonavir) has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether acute use of Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30–180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 28, 2023. For those who had at least 1 risk factor for severe COVID-19 illness, 159,659 were treated with at least one dose of Paxlovid within 5 days since infection and 272,048 were not treated with Paxlovid or other COVID-19 treatments during the acute infection period. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. High-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.

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Cite

BibTeXRIS
BibTeX
@article{wang2026realworld,
  title = {{Real-world effectiveness of Paxlovid in protecting Long COVID for outpatient adult patients: A target trial emulation study from the RECOVER Initiative}},
  author = {Fei Wang and Haoyang Li and Dhruv Khullar and Yongkang Zhang and Stephenson Strobel and Yong Chen and Marc A. Sala and Payal B. Patel and Alejandro P. Comellas and Andrew Wylam and Mark Weiner and Chris B. Forrest and Thomas W. Carton and Fei Wang and Rainu Kaushal},
  journal = {PLOS Global Public Health},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pgph.0005771},
  url = {https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0005771},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Real-world effectiveness of Paxlovid in protecting Long COVID for outpatient adult patients: A target trial emulation study from the RECOVER Initiative
AU  - Fei Wang
AU  - Haoyang Li
AU  - Dhruv Khullar
AU  - Yongkang Zhang
AU  - Stephenson Strobel
AU  - Yong Chen
AU  - Marc A. Sala
AU  - Payal B. Patel
AU  - Alejandro P. Comellas
AU  - Andrew Wylam
AU  - Mark Weiner
AU  - Chris B. Forrest
AU  - Thomas W. Carton
AU  - Fei Wang
AU  - Rainu Kaushal
PY  - 2026
DA  - 2026/10/28
JO  - PLOS Global Public Health
DO  - 10.1371/journal.pgph.0005771
UR  - https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0005771
AB  - Paxlovid (nirmatrelvir/ritonavir) has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether acute use of Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30–180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 28, 2023. For those who had at least 1 risk factor for severe COVID-19 illness, 159,659 were treated with at least one dose of Paxlovid within 5 days since infection and 272,048 were not treated with Paxlovid or other COVID-19 treatments during the acute infection period. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. High-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.
SN  - 2767-3375
ER  -