Int J Infect Dis . CCR5 Inhibition in Critical COVID-19 Patients Decreases Inflammatory Cytokines, Increases CD8 T-Cells, and Decreases SARS-CoV2 RNA in Plasma by Day 14

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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

Free PMC article

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.