ArticleNature communications2024
A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- A Viroimmunologic Model to Characterize the Antiviral Effect of Molnupiravir in Outpatients Infected With SARS-CoV-2: Implication for Treatment Duration.The Journal of infectious diseases · 2025Trial
- Transmission of mutated SARS-CoV-2 variants is favored by relatively prolonged infections due to delayed immunity.bioRxiv : the preprint server for biology · 2026Article
- Is it "Time to Eliminate" Time to Elimination of Symptoms as a Primary Trial End Point for Drugs Targeting Respiratory Viruses?The Journal of infectious diseases · 2026Article
- COVID-19 Rebound in Nirmatrelvir Plus Ritonavir Treatment and Control Groups: Prospective Cohort Study.Interactive journal of medical research · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Strategies for mitigating severe COVID-19 in patients with haematological malignancy during the omicron era.The Journal of antimicrobial chemotherapy · 2026Review
- Viral kinetics in adults with Covid-19 treated with nirmatrelvir-ritonavir or molnupiravir: a population-based, observational cohort study.Virology journal · 2026Observational
- Review
- Viral Dynamic Models During COVID-19: Are We Ready for the Next Pandemic?CPT: pharmacometrics & systems pharmacology · 2025Review
- Using virtual patient cohorts to uncover immune response differences in cancer and immunosuppressed COVID-19 patients.PLoS computational biology · 2025Article
- Intracellular and extracellular dynamics of herpes simplex virus 1 DNA and infectious particles in epithelial and neuronal cells.bioRxiv : the preprint server for biology · 2025Article
- Incidence of COVID-19 Symptom Rebound After Treatment with Remdesivir.Infectious disease reports · 2025Article
- Management of SARS-CoV-2 Infection-Clinical Practice Guidelines of the Polish Association of Epidemiologists and Infectiologists, for 2025.Journal of clinical medicine · 2025Review
- Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance.Journal of virology · 2025Article
- A consensus mathematical model of vaccine-induced antibody dynamics for multiple vaccine platforms and pathogens.Frontiers in immunology · 2025Article
- A theory for viral rebound after antiviral treatment: A study case for SARS-CoV-2.Mathematical biosciences · 2025Article
- Meeting report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20-24, 2024, organized by the International Society for Antiviral Research.Antiviral research · 2024Article
- Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance.bioRxiv : the preprint server for biology · 2024Article
- A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy.Nature communications · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir's in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.