CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14.
CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14.
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DOI：
10.1016/j.ijid.2020.10.101
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Sacha JB
中科院分区：
文献类型：
--
作者：
Patterson BK;Seethamraju H;Dhody K;Corley MJ;Kazempour K;Lalezari J;Pang APS;Sugai C;Mahyari E;Francisco EB;Pise A;Rodrigues H;Wu HL;Webb GM;Park BS;Kelly S;Pourhassan N;Lelic A;Kdouh L;Herrera M;Hall E;Bimber BN;Plassmeyer M;Gupta R;Alpan O;O'Halloran JA;Mudd PA;Akalin E;Ndhlovu LC;Sacha JB
感染严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）现已成为全球大流行。新出现的结果表明免疫反应失调。考虑到CCR5在免疫细胞迁移和炎症中的作用，我们研究了通过CCR5特异性抗体莱仑单抗阻断CCR5对重症COVID-19患者临床、免疫学和病毒学参数的影响。2020年3月，10名COVID-19晚期危重患者根据个人紧急使用指征接受了两剂莱仑单抗治疗。我们分析了治疗前和治疗后14天的临床表现、免疫细胞群、炎症以及SARS-CoV-2血浆病毒血症的变化。在14天的研究期间，6例患者存活，2例拔管，1例出院。我们观察到所有供体在第7天完全占据CCR5受体。与基线相比，我们观察到血浆IL-6降低，CD4/CD8比值恢复，SARS-CoV2血浆病毒血症（pVL）消退，具有统计学意义。此外，CD8百分比的增加与pVL的降低呈负相关（r = - 0.77, p = 0.0013）。我们的研究设计排除了临床疗效推断，但结果表明CCR5是COVID-19的治疗靶点，它们构成了正在进行的随机临床试验的基础。
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. Emerging results indicate a dysregulated immune response. Given the role of CCR5 in immune cell migration and inflammation, we investigated the impact of CCR5 blockade via the CCR5-specific antibody leronlimab on clinical, immunological, and virological parameters in severe COVID-19 patients. In March 2020, 10 terminally ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication. We analyzed changes in clinical presentation, immune cell populations, inflammation, as well as SARS-CoV-2 plasma viremia before and 14 days after treatment. Over the 14-day study period, six patients survived, two were extubated, and one discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared with the baseline, we observed a concomitant statistically significant reduction in plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL). Furthermore, the increase in the CD8 percentage was inversely correlated with the reduction in pVL (r = −0.77, p = 0.0013). Our study design precludes clinical efficacy inferences but the results implicate CCR5 as a therapeutic target for COVID-19 and they form the basis for ongoing randomized clinical trials.
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