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SARS-CoV-2 Omicron variants and their susceptibility towards Monoclonal Antibodies in a Swedish cohort during 2022-23, studied by next-generation sequencing

Haars, Jonathan
; 
Palanisamy, Navaneethan
; 
Wallin, Frans
; 
Mölling, Paula
; 
Lindh, Johan
; 
Sundqvist, Martin
; 
Ellström, Patrik
; 
Kaden, René
; 
Lennerstrand, Johan
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Uppsala University; University of Chester; Örebro University Hospital; Örebro University; SciLifeLab, Clinical Genomics Uppsala
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2023-09-12
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Chester Medical School
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Abstract
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 next-generation sequencing, mainly with the Nanopore sequencing method. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. 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). SARS-CoV-2 Omicron variants and their susceptibility towards Monoclonal Antibodies in a Swedish cohort during 2022-23, studied by next-generation sequencing. Prepints.org. https://doi.org/10.20944/preprints202309.0748.v1
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Prepints.org
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http://hdl.handle.net/10034/629494
DOI
10.20944/preprints202309.0748.v1
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Preprint
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https://www.preprints.org/manuscript/202309.0748/v1