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Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment

Focosi et al., Drug Resistance Updates, doi:10.1016/j.drup.2023.100991
Aug 2023  
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Review of reports of treatment-emergent resistance to COVID-19 monoclonal antibodies (mAbs), showing that some post-mAb treatment mutations appeared to spread globally soon after the mAb was introduced, raising concerns about transmission from treated patients. Treatment-emergent resistance was common, occurring in 10-50% of patients, with most events in immunocompromised patients.
This study includes bamlanivimab/etesevimab, casirivimab/imdevimab, tixagevimab/cilgavimab, sotrovimab, and bebtelovimab.
Focosi et al., 10 Aug 2023, Italy, peer-reviewed, 4 authors.
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Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment
Daniele Focosi, Scott Mcconnell, David J Sullivan, Arturo Casadevall
The mutation rate of the Omicron sublineage has led to baseline resistance against all previously authorized anti-Spike monoclonal antibodies (mAbs). Nevertheless, in case more antiviral mAbs will be authorized in the future, it is relevant to understand how frequently treatment-emergent resistance has emerged so far, under different combinations and in different patient subgroups. We report the results of a systematic review of the medical literature for case reports and case series for treatment-emergent immune escape, which is defined as emergence of a resistance-driving mutation in at least 20% of sequences in a given host at a given timepoint. We identified 31 publications detailing 201 cases that included different variants of concern (VOC) and found that the incidence of treatment emergentresistance ranged from 10% to 50%. Most of the treatment-emergent resistance events occurred in immunocompromised patients. Interestingly, resistance also emerged against cocktails of two mAbs, albeit at lower frequencies. The heterogenous therapeutic management of those cases doesn't allow
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