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

Int J Infect Dis. 2021 Feb;103:25-32. doi: 10.1016/j.ijid.2020.10.101. Epub 2020 Nov 10.

Abstract

Objective: 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.

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.

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.

Keywords: CCR5; COVID-19; Immunotherapy; Leronlimab; Plasma viral load.

MeSH terms

  • Adult
  • Aged
  • CCR5 Receptor Antagonists / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / drug therapy*
  • COVID-19 / immunology
  • COVID-19 / virology
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood*
  • SARS-CoV-2*
  • Time Factors

Substances

  • CCR5 Receptor Antagonists
  • Cytokines
  • RNA, Viral