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

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, Monica HerreraEric Hall, Benjamin N. Bimber, Matthew Plassmeyer, Raavi Gupta, Oral Alpan, Jane A. O'Halloran, Philip A. Mudd, Enver Akalin, Lishomwa C. Ndhlovu, Jonah B. Sacha

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalInternational Journal of Infectious Diseases
Volume103
DOIs
StatePublished - Feb 2021
Externally publishedYes

Keywords

  • CCR5
  • COVID-19
  • Immunotherapy
  • Leronlimab
  • Plasma viral load

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14'. Together they form a unique fingerprint.

Cite this