在固体器官移植接收者中,SARS-CoV-2尖端密码突变和抗尖端单克隆抗体治疗后住院的风险
Zachary A Yetmar1, Joseph D Yao2, Raymund R Razonable1,3
1Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Journal of medical virology
|June 19, 2023
概括
针对COVID-19的单克隆抗体 (mAb) 治疗是有效的,但SARS-CoV-2变种可以发展突变突变,降低抗体易感性. 这些突变并没有预测mAbs.治疗的移植患者的住院治疗.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
背景情况:
- 中和抗单克隆抗体 (mAb) 疗法在预防COVID-19住院治疗方面表现出高效.
- 新出现的SARS-CoV-2变种可能具有减少体外抗体易感性的尖端蛋白突变.
- 这些尖端蛋白突变对治疗结果的临床影响仍然不完全理解.
研究的目的:
- 调查SARS-CoV-2尖端突变之间的关联,在实验室中降低了mAb敏感性和固体器官移植接受者的临床结果.
- 为了确定特定的尖码子突变是否预测在治疗抗尖mAb疗法治疗轻度至中度COVID-19的患者住院治疗.
主要方法:
- 一项对实体器官移植接受者进行病例控制研究,这些接受者因COVID-19而接受了mAb.Ab抗药治疗.
- 从初始诊断进行了SARS-CoV-2分离物的基因型测序.
- 患者被归类为具有抗药性病毒,如果他们的隔离物具有尖端子突变,从而使体外对给药的mAb敏感性至少下降了五倍.
主要成果:
- 总体而言,22%的患者 (41人中有9人) 患有SARS-CoV-2,至少有一种尖端突变导致mAb易感性降低.
- 在接受索特罗维马布的患者中,12名中有9名患有S371L突变,预计会导致敏感性降低9.7倍.
- 在22名住院患者中的5名和19名非住院对照中的4名患者中存在抗药性突变,没有统计学上显著的差异 (p > 0.99).
结论:
- 在SARS-CoV-2分离物中,尖码子突变在体外降低了对抗尖mAbs的敏感性,这种突变在SARS-CoV-2分离物中很普遍.
- 包括S371L在内的突变,敏感性降低了9.7倍,并没有预测接下来住院治疗的固体器官移植接受者接受抗 mAb治疗.
- 目前的发现表明,在这种人群中,体外mAb敏感性降低不一定与临床治疗失败相关.
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