CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14

到第 14 天,重症 COVID-19 患者中 CCR5 抑制可减少炎症细胞因子、增加 CD8 T 细胞并降低血浆中的 SARS-CoV2 RNA

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作者:Bruce K Patterson, Harish Seethamraju, Kush Dhody, Michael J Corley, Kazem Kazempour, Jay Lalezari, Alina P S Pang, Christopher Sugai, Eisa Mahyari, Edgar B Francisco, Amruta Pise, Hallison Rodrigues, Helen L Wu, Gabriela M Webb, Byung S Park, Scott Kelly, Nader Pourhassan, Alina Lelic, Lama Kdouh, 

Conclusions

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.

Methods

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.

Objective

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. Emerging

Results

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). Conclusions: 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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