Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease MESHD 2019 (COVID-19), is now pandemic with nearly three million cases reported to date1. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease MESHD with pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD (ARDS) requiring mechanical ventilation2. Emerging results indicate a dysregulated immune response characterized by runaway inflammation MESHD, including cytokine release syndrome MESHD (CRS), as the major driver of pathology in severe COVID-193,4. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation MESHD in severe disease MESHD caused by SARS-CoV-2 infection MESHD are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma SERO IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Following compassionate care treatment with the CCR5 blocking antibody SERO leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma SERO IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Consistent with reduction of plasma SERO IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation MESHD, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma SERO viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.