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.
【저자키워드】 COVID-19, Immunotherapy, CCR5, Leronlimab, Plasma viral load., 【초록키워드】 Treatment, SARS-CoV-2, Inflammation, coronavirus, SARS-CoV2, antibody, IL-6, Immunotherapy, severe acute respiratory syndrome Coronavirus, CD8, global pandemic, Migration, Viral, Viremia, Viral load, Patient, Study design, plasma, respiratory, randomized clinical trials, CCR5, Donor, Emergency use, Clinical efficacy, dose, Immune cell, therapeutic target, Receptor occupancy, acute respiratory syndrome, Virological, Inference, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, study period, severe COVID-19 patients, dysregulated immune response, restoration, blockade, CD4/CD8, parameter, over, immune cell populations, Complete, immunological, statistically significant reduction, analyzed, investigated, changes in, correlated, increase in, reduction in, discharged, survived, baseline, critical COVID-19 patient, 【제목키워드】 SARS-CoV2, T-cells, CD8, RNA, plasma, Inflammatory cytokines, decrease, increase, critical COVID-19 patient,