Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan:379:109339.
doi: 10.1016/j.mbs.2024.109339. Epub 2024 Nov 20.

A theory for viral rebound after antiviral treatment: A study case for SARS-CoV-2

Mara Perez  1 , Marcelo Actis  2 , Ignacio Sanchez  3 , Esteban A Hernandez-Vargas  4 , Alejandro H González  3
Affiliations

A theory for viral rebound after antiviral treatment: A study case for SARS-CoV-2

Mara Perez et al. Math Biosci. 2025 Jan.

Abstract

A fraction of individuals infected with SARS-CoV-2 experienced rebounds when treated with effective antivirals such as Nirmatrelvir/Ritonavir (Paxlovid). Although this phenomenon has been studied from biological and statistical perspectives, the underlying dynamical mechanism is not yet fully understood. In this work, we characterize the dynamic behavior of a target-cell model to explain post-treatment rebounds from the perspective of set-theoretic stability analysis. Without relying on the effects of the adaptive immune system or the resistance through viral mutations, we develop mathematical conditions for antiviral treatments to avoid viral rebound. Simulation results illustrate the critical role of dosage (i.e., the doses and timing of administration) in taking advantage of highly effective drugs and tailoring therapies.

Keywords: Antiviral treatment; In-host infection; Rebound threshold; Viral rebound.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Similar articles

See all similar articles

References

    1. Ke R, Zitzmann C, Ho DD, Ribeiro RM, Perelson AS, In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness, Proceedings of the National Academy of Sciences 118 (49) (2021). - PMC - PubMed
    1. Kozlov M, Covid drug paxlovid was hailed as a game-changer. What happened?, Nature (2023). - PubMed
    1. Edelstein GE, Boucau J, Uddin R, Marino C, Liew MY, Barry M, Choudhary MC, Gilbert RF, Reynolds Z, Li Y, et al. , SARS-CoV-2 virologic rebound with nirmatrelvir–ritonavir therapy: an observational study, Annals of Internal Medicine 176 (12) (2023) 1577–1585. - PMC - PubMed
    1. Pandit JA, Radin JM, Chiang D, Spencer E, Pawelek J, Diwan M, Roumani L, Mina M, The paxlovid rebound study: a prospective cohort study to evaluate viral and symptom rebound differences between paxlovid and untreated COVID-19 participants, medRxiv (2022) 2022–11. - PMC - PubMed
    1. Cohen MS, Brown ER, Rebound of COVID-19 with nirmatrelvir– ritonavir antiviral therapy, Annals of Internal Medicine 176 (12) (2023) 1672–1673. - PMC - PubMed

LinkOut - more resources