التفاصيل البيبلوغرافية
| العنوان: |
Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy. |
| المؤلفون: |
Choudhary MC, Chew KW, Deo R, Flynn JP, Regan J, Crain CR, Moser C, Hughes M, Ritz J, Ribeiro RM, Ke R, Dragavon JA, Javan AC, Nirula A, Klekotka P, Greninger AL, Fletcher CV, Daar ES, Wohl DA, Eron JJ, Currier JS, Parikh UM, Sieg SF, Perelson AS, Coombs RW, Smith DM, Li JZ |
| مؤلفون مشاركون: |
ACTIV-2/A5401 Study Team |
| المصدر: |
MedRxiv : the preprint server for health sciences [medRxiv] 2021 Sep 15. Date of Electronic Publication: 2021 Sep 15. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Resistance mutations to monoclonal antibody (mAb) therapy has been reported, but in the non-immunosuppressed population, it is unclear if in vivo emergence of SARS-CoV-2 resistance mutations alters either viral replication dynamics or therapeutic efficacy. In ACTIV-2/A5401, non-hospitalized participants with symptomatic SARS-CoV-2 infection were randomized to bamlanivimab (700mg or 7000mg) or placebo. Treatment-emergent resistance mutations were significantly more likely detected after bamlanivimab 700mg treatment than placebo (7% of 111 vs 0% of 112 participants, P=0.003). There were no treatment-emergent resistance mutations among the 48 participants who received bamlanivimab 7000mg. Participants with emerging mAb resistant virus had significantly higher pre-treatment nasopharyngeal and anterior nasal viral load. Intensive respiratory tract viral sampling revealed the dynamic nature of SARS-CoV-2 evolution, with evidence of rapid and sustained viral rebound after emergence of resistance mutations, and worsened symptom severity. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest and associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment, resulting in prolonged high level respiratory tract viral loads and clinical worsening. Careful virologic assessment should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19. |
| معلومات مُعتمدة: |
R01 OD011095 United States OD NIH HHS; UL1 TR002548 United States TR NCATS NIH HHS; R01 AI028433 United States AI NIAID NIH HHS; UM1 AI069463 United States AI NIAID NIH HHS; UM1 AI068636 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20210921 Latest Revision: 20230829 |
| رمز التحديث: |
20230830 |
| مُعرف محوري في PubMed: |
PMC8452115 |
| DOI: |
10.1101/2021.09.03.21263105 |
| PMID: |
34545376 |
| قاعدة البيانات: |
MEDLINE |
