Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023
Authors
Haars, JonathanPalanisamy, Navaneethan
Wallin, Frans
Mölling, Paula
Lindh, Johan
Sundqvist, Martin
Ellström, Patrik
Kaden, René
Lennerstrand, Johan
Affiliation
Uppsala University; University of Chester; Örebro University Hospital; SciLifeLab, UppsalaPublication Date
2023-09-27
Metadata
Show full item recordAbstract
Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study, 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden, collected between March 2022 and May 2023, were whole-genome sequenced using amplicon-based sequencing methods on Oxford Nanopore GridION, Illumina MiSeq, Illumina HiSeq, or MGI DNBSEQ-G400 instruments. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. We found that the dominant sublineages changed over time, and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.Citation
Haars, J., Palanisamy, N., Wallin, F., Mölling, P., Lindh, J., Sundqvist, M., Ellström, P., Kaden, R., & Lennerstrand, J. (2023). Prevalence of SARS-CoV-2 Omicron sublineages and spike protein mutations conferring resistance against monoclonal antibodies in a Swedish cohort during 2022–2023. Microorganisms, 11(10), article-number 2417. https://doi.org/10.3390/microorganisms11102417Publisher
MDPIJournal
MicroorganismsAdditional Links
https://www.mdpi.com/2076-2607/11/10/2417Type
ArticleEISSN
2076-2607ae974a485f413a2113503eed53cd6c53
10.3390/microorganisms11102417
Scopus Count
Collections
Except where otherwise noted, this item's license is described as Licence for VoR version of this article: https://creativecommons.org/licenses/by/4.0/