Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance
Nirmatrelvir-ritonavir is an effective treatment for SARS-CoV-2. In a subset of individuals treated with nirmatrelvir-ritonavir, the initial reduction in viral load is followed by viral rebound once treatment is stopped. We show that the timing of treatment initiation with nirmatrelvir-ritonavir may influence the risk of viral rebound. Nirmatrelvir-ritonavir stops viral growth and preserves target cells but may not lead to full clearance of the virus. Thus, once treatment ends, if an effective adaptive immune response has not adequately developed, the remaining virus can lead to rebound. Our results provide insights into the mechanisms of rebound and can help develop better treatment strategies to minimize this possibility.
Authors
- Mark Jacob Siedner (ORCID: https://orcid.org/0000-0003-3506-842X)
- Rockib Uddin (ORCID: https://orcid.org/0000-0001-5953-1234)
- Yumeko Kawano (ORCID: https://orcid.org/0000-0003-2423-5982)
- Zachary S. Wallace (ORCID: https://orcid.org/0000-0003-4708-7038)
- May Y. Liew
- Jeffrey A. Sparks (ORCID: https://orcid.org/0000-0002-5556-4618)
- Jacob E. Lemieux (ORCID: https://orcid.org/0000-0002-2758-4005)
- Ruy M. Ribeiro (ORCID: https://orcid.org/0000-0002-3988-8241)
- Sarah P. Hammond (ORCID: https://orcid.org/0000-0002-4271-7443)
- Jonathan Z. Li (ORCID: https://orcid.org/0000-0001-9914-9662)
- Tin Phan (ORCID: https://orcid.org/0000-0001-9998-8263)
- Amy K. Barczak (ORCID: https://orcid.org/0000-0003-3806-2381)
- Alan S. Perelson (ORCID: https://orcid.org/0000-0002-2455-0002)
- Caitlin Marino
- Julie Boucau (ORCID: https://orcid.org/0000-0001-6731-7238)
- Zahra Reynolds (ORCID: https://orcid.org/0000-0003-0668-6798)
- Manish C. Choudhary (ORCID: https://orcid.org/0000-0002-3192-7840)
- Mamadou Barry (ORCID: https://orcid.org/0009-0005-1458-2528)
- Tammy D. Vyas
- Jatin M. Vyas (ORCID: https://orcid.org/0000-0002-9985-9565)
- Yijia Li (ORCID: https://orcid.org/0000-0001-5300-0571)
- Shruti Sagar
- Gregory E. Edelstein
- Karry Su
- Dessie Tien
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Santa Fe Institute (US)
- Los Alamos National Laboratory (US)
- Harvard University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Massachusetts General Hospital (US)
- Africa Health Research Institute (ZA)
- University of Pittsburgh Medical Center (US)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1128/jvi.01623-24
- Citations
- 12
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 16.75
Funders
- Massachusetts General Hospital
- Massachusetts Consortium on Pathogen Readiness
- National Institutes of Health
- Laboratory Directed Research and Development
- Los Alamos National Laboratory