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Development of Resistance-Associated Mutations After Sotrovimab Administration in High-risk Individuals Infected With the SARS-CoV-2 Omicron Variant

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME

The SARS-CoV-2 Omicron variant of concern is currently the dominant variant circulating globally. Sotrovimab is among the few monoclonal antibodies that has retained its neutralizing activity against Omicron/BA.1 and received Emergency Use Authorization for treatment of patients at risk for progression to severe disease.1,2

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Article Information

Accepted for Publication: July 25, 2022.

Published Online: August 1, 2022. doi:10.1001/jama.2022.13854

Corresponding Author: Emma Birnie, MD, PhD, Center for Experimental and Molecular Medicine, Meibergdreef 9, Amsterdam, the Netherlands (e.birnie@amsterdamumc.nl).

Author Contributions: Drs Birnie and Wiersinga had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Birnie and Biemond contributed equally.

Concept and design: Birnie, de Bree, Welkers, Wiersinga.

Acquisition, analysis, or interpretation of data: Birnie, Biemond, Appelman, Jonges, Welkers, Wiersinga.

Drafting of the manuscript: Birnie, Biemond, Welkers, Wiersinga.

Critical revision of the manuscript for important intellectual content: Birnie, Biemond, Appelman, Jonges, Welkers, Wiersinga.

Statistical analysis: Birnie, Biemond, Welkers.

Obtained funding: de Bree, Wiersinga.

Administrative, technical, or material support: Birnie, Biemond, Appelman, Jonges, Welkers.

Supervision: Birnie, Wiersinga.

Conflict of Interest Disclosures: Dr Wiersinga reported receiving grant support (grant 91716475) from the Netherlands Organization of Scientific Research and personal fees (fees paid to his institution) from GlaxoSmithKline, Pfizer, Sobi, and AstraZeneca. No other disclosures were reported.

Funding/Support: This study was funded by grant 10430142110001 from the Netherlands Organization for Health Research and Development.

Role of the Funder/Sponsor: The Netherlands Organization for Health Research and Development had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the physicians, nurses, and other health care clinicians at the Amsterdam University Medical Centers and all the patients who participated in this study. The research presented is part of a Dutch cohort study on neutralizing monoclonal antibodies against and other antiviral agents against SARS-CoV-2 (TURN-COVID; NCT05195060). Additional contributions appear in the Supplement.

References
1.
Wiersinga  WJ , Rhodes  A , Cheng  AC ,  et al.  Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19).   JAMA. 2020;324(8):782-793.PubMedGoogle ScholarCrossref
2.
Gupta  A , Gonzalez-Rojas  Y , Juarez  E ,  et al.  Effect of sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19.   JAMA. 2022;327(13):1236-1246.PubMedGoogle ScholarCrossref
3.
Corey  L , Beyrer  C , Cohen  MS ,  et al.  SARS-CoV-2 variants in patients with immunosuppression.   N Engl J Med. 2021;385(6):562-566. PubMedGoogle ScholarCrossref
4.
Rockett  R , Basile  K , Maddocks  S ,  et al.  Resistance mutations in SARS-CoV-2 Delta variant after sotrovimab use.   N Engl J Med. 2022;386(15):1477-1479. PubMedGoogle ScholarCrossref
5.
Cameroni  E , Bowen  JE , Rosen  LE ,  et al.  Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.   Nature. 2022;602(7898):664-670.PubMedGoogle ScholarCrossref
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