دورية أكاديمية
Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2.
| العنوان: | Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2. |
|---|---|
| المؤلفون: | Choudhary MC; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Deo R; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Evering TH; Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Chew KW; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Giganti MJ; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Moser C; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Ritz J; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Regan J; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Flynn JP; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Crain CR; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Wohl DA; Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA., Currier JS; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Eron JJ; Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA., Margolis D; Brii Biosciences, Durham, North Carolina, USA., Zhu Q; Brii Biosciences, Durham, North Carolina, USA., Zhon L; Brii Biosciences, Durham, North Carolina, USA., Ya L; Brii Biosciences, Durham, North Carolina, USA., Greninger AL; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Hughes MD; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Smith D; Department of Medicine, University of California, San Diego, La Jolla, California, USA., Daar ES; Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA., Li JZ; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
| المصدر: | The Journal of infectious diseases [J Infect Dis] 2024 Aug 16; Vol. 230 (2), pp. 394-402. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press |
| مواضيع طبية MeSH: | SARS-CoV-2*/immunology , SARS-CoV-2*/drug effects , Viral Load*/drug effects , Antibodies, Monoclonal, Humanized*/therapeutic use , Antibodies, Monoclonal, Humanized*/pharmacology , COVID-19 Drug Treatment*, Humans ; Female ; Male ; Middle Aged ; Drug Resistance, Viral ; Antiviral Agents/therapeutic use ; Antiviral Agents/pharmacology ; COVID-19/immunology ; COVID-19/virology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/immunology ; Aged ; Adult ; Drug Therapy, Combination |
| مستخلص: | Background: Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs. Methods: Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant. Results: Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death. Conclusions: Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance. Competing Interests: Potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| References: | Mol Biol Evol. 2022 Feb 3;39(2):. (PMID: 35038741) Cell. 2021 Jun 10;184(12):3086-3108. (PMID: 34087172) Nat Rev Immunol. 2021 Jun;21(6):382-393. (PMID: 33875867) Cell Rep. 2022 May 17;39(7):110812. (PMID: 35568025) Virus Evol. 2022 May 11;8(1):veac021. (PMID: 35573973) BMC Infect Dis. 2021 Dec 7;21(1):1223. (PMID: 34876033) Nature. 2020 Aug;584(7819):115-119. (PMID: 32454513) N Engl J Med. 2019 Dec 12;381(24):2293-2303. (PMID: 31774950) Clin Microbiol Infect. 2023 Feb;29(2):240-246. (PMID: 36067943) J Clin Invest. 2023 Mar 15;133(6):. (PMID: 36727404) Nature. 2022 Aug;608(7923):603-608. (PMID: 35790190) Nature. 2021 Apr;592(7853):277-282. (PMID: 33545711) Nat Rev Microbiol. 2023 Mar;21(3):162-177. (PMID: 36653446) Front Immunol. 2022 Sep 14;13:980435. (PMID: 36189212) N Engl J Med. 2022 Jun 9;386(23):2188-2200. (PMID: 35443106) J Infect Dis. 2001 Aug 1;184(3):350-4. (PMID: 11443562) Cell. 2021 Apr 1;184(7):1821-1835.e16. (PMID: 33667349) Ann Intern Med. 2023 May;176(5):658-666. (PMID: 37068272) N Engl J Med. 2021 Jan 21;384(3):229-237. (PMID: 33113295) N Engl J Med. 2004 Mar 4;350(10):1023-35. (PMID: 14999114) J Antimicrob Chemother. 2021 May 12;76(6):1558-1563. (PMID: 33693678) Nat Rev Drug Discov. 2022 Sep;21(9):676-696. (PMID: 35725925) JAMA. 2021 Feb 16;325(7):632-644. (PMID: 33475701) Lancet Reg Health Eur. 2021 Sep;8:100164. (PMID: 34278371) Nat Commun. 2020 Oct 30;11(1):5493. (PMID: 33127906) Proc Natl Acad Sci U S A. 2022 Mar 1;119(9):. (PMID: 35165203) Ann Intern Med. 2023 Mar;176(3):348-354. (PMID: 36802755) N Engl J Med. 2021 Nov 18;385(21):1941-1950. (PMID: 34706189) Nat Microbiol. 2022 Nov;7(11):1906-1917. (PMID: 36289399) Clin Infect Dis. 2023 Feb 8;76(3):e507-e509. (PMID: 35867699) Nat Rev Microbiol. 2023 Feb;21(2):112-124. (PMID: 36307535) J Biomed Sci. 2022 Jan 4;29(1):1. (PMID: 34983527) N Engl J Med. 2021 Jan 21;384(3):238-251. (PMID: 33332778) PLoS One. 2022 Mar 9;17(3):e0261045. (PMID: 35263335) N Engl J Med. 2021 Oct 7;385(15):1382-1392. (PMID: 34260849) N Engl J Med. 2020 Dec 3;383(23):2291-2293. (PMID: 33176080) J Clin Virol. 2020 Aug;129:104474. (PMID: 32504946) |
| معلومات مُعتمدة: | National Institute of Allergy and Infectious Diseases; UM1 AI068634 United States AI NIAID NIH HHS; UM1 AI069481 United States AI NIAID NIH HHS; UM1 AI106701 United States AI NIAID NIH HHS; UM1 AI069419 United States AI NIAID NIH HHS; UM1 AI068636 United States AI NIAID NIH HHS; UM1AI068634 United States NH NIH HHS; UM1 AI069424 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: SARS-CoV-2; mAb resistance; variants; viral kinetics |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal, Humanized) 0 (Antiviral Agents) 0 (Antibodies, Monoclonal) |
| SCR Organism: | SARS-CoV-2 variants |
| تواريخ الأحداث: | Date Created: 20240508 Date Completed: 20240815 Latest Revision: 20240919 |
| رمز التحديث: | 20240919 |
| مُعرف محوري في PubMed: | PMC11326811 |
| DOI: | 10.1093/infdis/jiae192 |
| PMID: | 38716969 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1537-6613 |
|---|---|
| DOI: | 10.1093/infdis/jiae192 |