Department of Infectious Disease, Gundersen Health System, La Crosse, WI, USA.
Kabara Cancer Research Institute, Gundersen Medical Foundation, La Crosse, WI, USA.
Diagn Microbiol Infect Dis. 2022 May;103(1):115656. doi: 10.1016/j.diagmicrobio.2022.115656. Epub 2022 Feb 3.
The implementation of monoclonal antibody therapeutics during the COVID-19 pandemic altered the selective pressures encountered by SARS-CoV-2, raising the possibility of selection for resistant variants. Within-host viral evolution was reported in treated immunocompromised individuals but whether this signifies a real risk of onward transmission is unclear. We used a regional SARS-CoV-2 sequencing program to monitor lineages with clinically relevant variants in identified patients, which facilitated analysis of parameters potentially relevant to new variant emergence. Here we describe a newly acquired spike E484K mutation detected within the B.1.311 lineage. Multiple individuals in 2 households of the same extended family were infected. The timing and patterns of spread were consistent with de novo emergence of this E484K variant in the bamlanivimab-treated index patient. Our study suggests that the selective pressures introduced by the widespread administration of these antibodies may warrant increased genomic surveillance to identify and mitigate spread of therapy-induced variants.
在 COVID-19 大流行期间,单克隆抗体治疗的实施改变了 SARS-CoV-2 所面临的选择压力,增加了出现耐药变异的可能性。在接受治疗的免疫功能低下个体中已报告了体内病毒进化,但这是否表明有进一步传播的实际风险尚不清楚。我们使用区域 SARS-CoV-2 测序计划来监测在已确定的患者中具有临床相关变异的谱系,这有助于分析与新变异出现相关的潜在参数。在这里,我们描述了在 B.1.311 谱系中检测到的新获得的刺突 E484K 突变。同一大家庭的 2 户家庭中的多个个体被感染。传播的时间和模式与 Bamlanivimab 治疗的指数患者中 E484K 变异的从头出现一致。我们的研究表明,这些抗体广泛应用所带来的选择压力可能需要增加基因组监测,以识别和减轻治疗诱导的变异的传播。