Int J Infect Dis
. 2020 Nov 10;S1201-9712(20)32305-5.
doi: 10.1016/j.ijid.2020.10.101. Online ahead of print.
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 1 , Harish Seethamraju 2 , Kush Dhody 3 , Michael J Corley 4 , Kazem Kazempour 3 , Jay Lalezari 5 , Alina P S Pang 4 , Christopher Sugai 6 , Eisa Mahyari 7 , Edgar B Francisco 8 , Amruta Pise 8 , Hallison Rodrigues 8 , Helen L Wu 7 , Gabriela M Webb 7 , Byung S Park 7 , Scott Kelly 9 , Nader Pourhassan 9 , Alina Lelic 10 , Lama Kdouh 10 , Monica Herrera 11 , Eric Hall 11 , Benjamin N Bimber 7 , Matthew Plassmeyer 12 , Raavi Gupta 13 , Oral Alpan 12 , Jane A O'Halloran 14 , Philip A Mudd 15 , Enver Akalin 2 , Lishomwa C Ndhlovu 4 , Jonah B Sacha 7
Affiliations
- PMID: 33186704
- PMCID: PMC7654230
- DOI: 10.1016/j.ijid.2020.10.101
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 patients with severe COVID-19 disease.
Methods: In March 2020, ten terminally-ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication (EIND). 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 6/10 patients survived, 2 extubated, and 1 patient was discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared to baseline, we observed a concomitant statistically significant reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL) compared to controls. Further, the increase in CD8% was inversely correlated with reduction in pVL (r = -0.77, p = 0.0013).
Conclusions: While the current study design precludes clinical efficacy inferences, these results implicate CCR5 as a therapeutic target for COVID-19 and form the basis for ongoing randomized clinical trials.
Keywords: CCR5; COVID-19; immunotherapy; leronlimab; plasma viral load.