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The monoclonal antibody sotrovimab, increasingly used worldwide as a cure because one of the few that maintains efficacy against the Omicron variant of Sars-CoV-2, could cause mutations in the virus. Research conducted by the Institute for Infectious Diseases of the University of Sydney in Australia reports that in patients treated with the antibody genetic changes in the pathogen that causes Covid-19, associated with the development of resistance to the drug itself. It is believed, the authors explain, that this is “the first time that resistance to sotrovimab has been discovered in the clinic. Although rare, this highlights the crucial role of surveillance.”
Sotrovimab neutralizes Sars-CoV-2 primarily by blocking its entry into the host cell by binding to a particular region of the virus’s Spike protein. The observational study conducted by Australian researchers is published in the ‘New England Journal of Medicine’ and took place during the Delta outbreak in 2021, analyzing the first 100 patients treated with the drug in western Sydney. Post-treatment follow-up was required in 23 patients, and of 8 of these who had remaining respiratory samples that could be used in genomic analysis, 4 developed resistant mutations. The data showed the persistence of viable SARS-CoV-2 in these patients after sotrovimab infusions and the rapid development of associated Spike gene mutations in in vitro drug resistance tests.
“We found that the virus can develop mutations within the patient several days after treatment with sotrovimab, which reduces the effectiveness of this treatment by more than 100 times,” explained lead author Rebecca Rockett, of the Sydney Institute. for Infectious Diseases. Mutations within the drug’s target site were discovered by analyzing the entire viral genome sequence before and after treatment. These mutations were detected in a “small number of patients” 6-13 days after treatment. “Samples of resistant viruses could easily be cultured in the laboratory, an indicator that individuals who develop resistance can transmit this resistant virus to others,” said senior research author Vitali Sintchenko.