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

Patterson, Bruce K.; Seethamraju, Harish; Dhody, Kush; Corley, Michael J.; Kazempour, Kazem; Lalezari, Jay; Pang, Alina P.S.; Sugai, Christopher; Mahyari, Eisa; Francisco, Edgar B.; Pise, Amruta; Rodrigues, Hallison; Wu, Helen L.; Webb, Gabriela M.; Park, Byung S.; Kelly, Scott; Pourhassan, Nader; Lelic, Alina; Kdouh, Lama; Herrera, Monica; Hall, Eric; Bimber, Benjamin N.; Plassmeyer, Matthew; Gupta, Raavi; Alpan, Oral; O’Halloran, Jane A.; Mudd, Philip A.; Akalin, Enver; Ndhlovu, Lishomwa C.; Sacha, Jonah B.

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.