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在接受巴美洛维单抗治疗的患者的家庭接触者中出现并传播 SARS-CoV-2 E484K 变异株。

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

机构信息

Department of Infectious Disease, Gundersen Health System, La Crosse, WI, USA.

Kabara Cancer Research Institute, Gundersen Medical Foundation, La Crosse, WI, USA.

出版信息

Diagn Microbiol Infect Dis. 2022 May;103(1):115656. doi: 10.1016/j.diagmicrobio.2022.115656. Epub 2022 Feb 3.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb63/8810429/047572a95b65/gr1_lrg.jpg

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