Acquisition and onward transmission of a SARS-CoV-2 E484K variant among household contacts of a bamlanivimab-treated patient

Abstract

The implementation of monoclonal antibody therapeutics during the COVID19 pandemic has altered the selective pressures encountered by SARS-CoV-2, raising the possibility of selection for variants resistant to one or more monoclonal antibodies and subsequent transmission into the wider population. Early studies indicated that monoclonal antibody treatment in immunocompromised individuals could result in within-host viral evolution preferentially affecting epitopes recognized by these antibodies, although whether this signifies a real risk of transmissible antibody resistant virus is unclear. In this study we have taken advantage of a regional SARS-CoV-2 genomic surveillance program encompassing regions in Wisconsin, Minnesota and Iowa to monitor the introduction or de novo emergence of SARS-Cov-2 lineages with clinically relevant variants. Here we describe a newly acquired E484K mutation in the SARS-CoV-2 spike protein detected within the B.1.311 lineage. Multiple individuals in two related households were infected. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient s quarantine period. Our study suggest that the selective pressures introduced by the now widespread administration of these antibodies may warrant increased genomic surveillance to identify and mitigate spread of therapy-induced variants.