[HTML][HTML] CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14
BK Patterson, H Seethamraju, K Dhody… - International Journal of …, 2021 - Elsevier
International Journal of Infectious Diseases, 2021•Elsevier
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 …
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 …
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.
Elsevier
