Covid treatment sotrovimab can cause drug-resistant mutation, study finds

Australian researchers raise concerns mutated virus could spread in the community if patients given the drug are not monitored

Melissa Davey Medical editor

Australian virologists have uncovered a drug-resistant mutation in the Covid-19 virus associated with the drug sotrovimab and say without the monitoring of patients given the treatment the mutated virus could spread in the community.

The world-first findings, published in the New England Journal of Medicine on Thursday, are the result of an analysis of the first 100 patients in western Sydney during the Delta outbreak in 2021 to be given sotrovimab.

Sotrovimab is a monoclonal antibody that is available in many countries to treat vulnerable patients who are at risk of severe disease and death due to Covid-19 infection. Sotrovimab must be administered via infusion within the first five days of Covid-19 infection, and prevents Covid-19 symptoms from becoming severe. It is one of the few human-engineered monoclonal antibodies that can target Omicron.

The lead author of the study, Dr Rebecca Rockett, said four of the patients developed resistance to sotrovimab six to 13 days after treatment. The whole genome sequence of the virus analysed from the patients before and after sotrovimab treatment uncovered mutations in a few patients that “made the drug effectively inactive,” Rockett, from the University of Sydney’s Institute for Infectious Diseases, said.

“We’re not sure if sotrovimab helps neutralise the virus early on in the infection before it develops resistance. But often drugs are given to treat Covid-19 patients and there’s not really any follow-up done. We realise that you can’t follow every patient with PCR testing or genomic surveillance, but we are trying to advocate for patients that progress to severe disease despite the treatment that we investigate using genomics to see whether they’ve acquired any resistance mutations.”

It was important to monitor them because once the patients acquired the mutations, Rockett and her team could still take samples from them and grow the virus in the laboratory, which meant they were still infectious. It meant the patients were at risk of passing the mutated virus on to others.

“What we don’t want to see is resistant virus disseminating in the community, because that will mean that a lot of other people can’t use this drug as well.”

Rockett said it would be prudent for those who developed resistance to isolate for longer until the virus had cleared, and make extra efforts to remain separate from those in the same household. The virus persisted in the affected patients for up to 24 days after sotrovimab treatment.

It marks the first report of resistance to sotrovimab in patients.

An infectious diseases physician and drug resistance expert with the Australian National University, Prof Peter Collignon, said potential spread of resistant viruses in the community presented “a real problem”.

“Thankfully, this mutation appears to be a relatively rare event, but the only way you ever know that is to keep an eye on it.”

GSK, the manufacturer of the drug, said the study results were consistent with its large clinical trials, which found a small proportion of patients develop on-treatment resistance.

Resistance is also seen in studies for other Covid-19 monoclonal antibodies and oral treatments, and relates to how the immune system interacts with the virus,” it said in a statement.

“This report does not change the positive benefit-risk of sotrovimab for use in the treatment of mild to moderate Covid-19 in patients at high risk of progression.”

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