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Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy

Choudhary et al., medRxiv, doi:10.1101/2021.09.03.21263105, NCT04518410
Sep 2021  
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20th treatment shown to reduce risk in May 2021
*, now known with p = 0.00029 from 20 studies, recognized in 4 countries. Efficacy is variant dependent.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments.
Analysis of ACTIV-2/A5401, showing the potential for rapid emergence of resistance during monoclonal antibody treatment, resulting in prolonged high level viral loads and clinical worsening. Treatment-emergent resistance mutations were more common after bamlanivimab 700mg (7% of 111 vs 0% of 112 participants, p=0.003).
Efficacy is highly variant dependent. In Vitro research suggests a lack of efficacy for omicron Haars, Liu, Pochtovyi, Sheward, VanBlargan.
Choudhary et al., 15 Sep 2021, preprint, 28 authors, trial NCT04518410 (history).
This PaperBamlaniv../e..All
Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy
Manish C Choudhary, Kara W Chew, Rinki Deo, James P Flynn, James Regan, Charles R Crain, Carlee Moser, Michael Hughes, Justin Ritz, Ruy M Ribeiro, Ruian Ke, Joan A Dragavon, Arzhang C Javan, Ajay Nirula, Paul Klekotka, Alexander L Greninger, Courtney V Fletcher, Eric S Daar, David A Wohl, Joseph J Eron, Judith S Currier, Urvi M Parikh, Scott F Sieg, Alan S Perelson, Robert W Coombs, MD Davey M Smith, MD Jonathan Z Li
All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Author contributions MCC, KC, RC, DMS, JZL conceptualized and performed the study, MCC, RD, JPF, JR, CC performed resistance analysis experiment; RMR, RK, ASP performed mathematical modeling; JD, AG performed viral load analysis; UP, SS performed serological analysis; CM, MH, JR performed statistical analysis.
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' '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. 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Late treatment
is less effective
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