A University of Sydney-led research firm in infectious diseases has reported genetic mutations in the virus that causes COVID-19, which are linked to the development of resistance to the drug Sotrovimab.
This is believed to be the first time that researchers have discovered clinical resistance to sotrovimab – although this is unusual, it highlights the important role of surveillance. Sotrovimab neutralizes SARS-CoV-2, which binds to a specific part of the SARS-CoV-2 mutant protein, preventing the virus from entering host cells.
The world’s first surveillance study, published in New England Journal of Medicinetook place during the Delta outbreak in 2021, analyzing the first 100 patients receiving Sotrovimab in western Sydney.
Twenty-three patients required postoperative follow-up, eight of whom developed residual respiratory specimens that could be used for genetic analysis, and four of these patients developed resistance mutations. The data suggest the potential for stabilization of SARS-CoV-2 in patients following administration of Sotrovimab and the rapid development of gene mutations associated with high levels of Sotrovimab resistance in vitro.
Lead author, Dr Rebecca Rockett from the Institute of Infectious Diseases, Sydney School of Medicine and Health, said with drug resistance developing in a small number of patients there is the potential to spread drug-resistant viruses.
Dr Rockett said: “We found that the virus that causes COVID-19 can develop mutations in a patient’s body a few days after treatment with Sotrovimab, which reduces the effectiveness of the treatment. This value is more than 100 times.
- The whole genome sequence of the virus that causes COVID-19 was analyzed from patients before and after treatment with Sotrovimab. Specific mutations in drug target sites have been detected that have previously been described to induce resistance in laboratory culture systems.
- Resistance to sotrovimab developed in a small number of patients 6 to 13 days after treatment.
- Resistant viruses can be cultured in laboratory culture systems, which is an indicator of viral fitness that the virus can be transmitted to others.
- Post-marketing genomic surveillance for new antiviral treatments is warranted to prevent unrecognized community spread of drug-resistant viruses.
- Using SARS-CoV-2 genomes available from around the world, the researchers demonstrated that although resistance mutations are extremely common, in Australia we know that they are particularly associated with treatment with sotrovimab.
- Lead author Professor Vitali Sintchenko says genomic surveillance requires caution not only to minimize the risk of treatment failure but also to the transmission of potentially resistant variants, as the virus remains undisturbed. persisted in patients for up to 24 days after treatment with Sotrovimab.
Professor Sintchenko, also from the Institute of Infectious Diseases Sydney, said: “Samples of the resistant virus can be easily cultured in the laboratory, an indication that individuals who develop resistance are more likely to develop resistance. can transmit drug-resistant viruses to others”.
This is the first report of resistance to Sotrovimab in clinical cases, supporting the findings of previous research, which demonstrated resistance-causing mutations to Sotrovimab in laboratory cultures and animal model.
The researchers in the new study sequenced the SARS-CoV-2 genome before patients were given the drug and then monitored them throughout the infection and were able to detect when resistance mutations drug in the viral genome becomes dominant.
The researchers then investigated millions of international SARS-CoV-2 (COVID-19) genomes to determine that this mutation is extremely rare.
Dr Rockett concludes: “The rapid increase in the use of monoclonal antibodies to treat COVID-19 requires a similar increase in monitoring for potential resistance mutations – which will help us detect resistance mutations earlier and prevent Sotrovimab, and other treatments, from becoming a victim of their own success.”
The paper includes co-authors from the University of Sydney Rebecca Rockett, Dominic Dwyer, Sharon Chen and Vitali Sintchenko, along with other coauthors from the Western Sydney Local Health District. WSLHD and the University of Sydney are part of the Westmead Health District, one of the largest health, education, research and training zones in Australia.