Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of
coronavirus disease 2019 (COVID-19), is now pandemic with nearly three million cases reported to date. Although the majority of
COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease with
pneumonia and
acute respiratory distress syndrome (ARDS) requiring
mechanical ventilation. Emerging results indicate a dysregulated immune response characterized by runaway
inflammation, including
cytokine release syndrome (CRS), as the major driver of pathology in severe
COVID-19. With no treatments currently approved for
COVID-19,
therapeutics to prevent or treat the excessive
inflammation in severe disease caused by
SARS-CoV-2 infection are urgently needed. Here, in 10 terminally-ill, critical
COVID-19 patients we report profound elevation of plasma
IL-6 and CCL5 (
RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma
viremia. Following compassionate care treatment with the CCR5 blocking antibody
leronlimab, we observed complete
CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma
IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma
viremia. Consistent with reduction of plasma
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, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma 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.