ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023
Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04401436 (COVID-19-Associated Lymphopenia Pathogenesis Study in Blood), which is not on this map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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.
COVID-19-Associated Lymphopenia Pathogenesis Study in Blood
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- SARS-CoV-2 infection rebound among patients receiving antiviral agents, convalescent plasma, or no treatment: a systematic review with meta-analysis.Blood transfusion = Trasfusione del sangue · 2024Pooled it
- Integrated virologic analysis of resistance to nirmatrelvir/ritonavir in individuals across four phase 2/3 clinical studies for the treatment of COVID-19.EBioMedicine · 2025Trial
- COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Post-steroid rebound in COVID-19 pneumonitis: a case series and review of the literature.BMC pulmonary medicine · 2025Review
- Prior SARS-CoV-2 infection affects adaptive immune responses to Omicron BA.4/BA.5 mRNA booster.The Journal of allergy and clinical immunology · 2025Article
- Risk Factors for Seeking Medical Care Following Nirmatrelvir-Ritonavir (Paxlovid) Treatment for COVID-19: "Symptom Rebound".Viruses · 2025Article
- 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
- Persistence of an Infectious Form of SARS-CoV-2 After Protease Inhibitor Treatment of Permissive Cells In Vitro.The Journal of infectious diseases · 2025Article
- Case Report: Simnotrelvir/Ritonavir are effective in shortening the course of prolonged SARS-CoV-2 infection during anti-CD20 maintenance therapy in patients with follicular lymphoma.Frontiers in oncology · 2025Article
- Diagnostic Utility of SARS-CoV-2 Nucleocapsid Antigenemia: A Meta-analysis.Open forum infectious diseases · 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
- Clinical rebound after treatment with nirmatrelvir/ritonavir in COVID-19.BMC infectious diseases · 2024Article
- A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy.Nature communications · 2024Article
- COVID-19 clinical rebound after treatment with nirmatrelvir/ritonavir.Research square · 2024Article
- A unifying model to explain high nirmatrelvir therapeutic efficacy against SARS-CoV-2, despite low post-exposure prophylaxis efficacy and frequent viral rebound.medRxiv : the preprint server for health sciences · 2024Article
- Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Review
- The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19.Pharmaceutics · 2024Review
- Immune responses to SARS-CoV-2 mRNA vaccination in people with idiopathic CD4 lymphopenia.The Journal of allergy and clinical immunology · 2024Article
- Association of Nirmatrelvir/Ritonavir Treatment and COVID-19-Neutralizing Antibody Titers in a Longitudinal Health Care Worker Cohort.Open forum infectious diseases · 2024Article
- Clinical Effectiveness of Ritonavir-Boosted Nirmatrelvir-A Literature Review.Advances in respiratory medicine · 2024Review
Corrections and comments
- Update of
Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNirmatrelvir/ritonavir, the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, reduces the risk of hospitalization and death by coronavirus disease 2019 (COVID-19) but has been associated with symptomatic rebound after therapy completion.
methodsSix individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti-receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed.
resultsHigh levels of SARS-CoV-2 anti-spike immunoglobulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2-specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4+ T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8.
conclusionsNirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatment courses. CLINICAL TRIALS REGISTRATION: NCT04401436.
Indexed as
Identifiers
What OpenQuestion holds
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.