Zarinsefat Arya, Hartoularos George, Rychkov Dmitry, Rashmi Priyanka, Chandran Sindhu, Vincenti Flavio, Yee Chun J, Sarwal Minnie M
Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States.
Front Genet. 2021 Jan 5;11:610682. doi: 10.3389/fgene.2020.610682. eCollection 2020.
COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at the single-cell level.
新型冠状病毒肺炎（COVID-19）对全球健康构成了重大威胁。早期数据显示，关键调节细胞因子白细胞介素-6（IL-6）在COVID-19的细胞因子风暴中起重要作用。因此，多项试验正在研究托珠单抗（一种抑制IL-6活性的IL-6受体抗体）对COVID-19治疗的效果，结果令人鼓舞。作为一项研究托珠单抗治疗对亚临床排斥反应的肾移植受者影响的临床试验的一部分，我们对托珠单抗治疗前后的刺激外周血单核细胞（PBMC）进行了单细胞RNA测序。我们利用这些数据创建了一个细胞因子风暴模型，以更好地了解托珠单抗在炎症存在时的作用。经托珠单抗治疗的细胞炎症介导基因和生物学途径的表达降低，尤其是在单核细胞中。这些结果支持了托珠单抗可能通过在单细胞水平上展示生物学影响来阻碍COVID-19细胞因子风暴的假说。
