@article{e4268a718fa54efe90add3425b231743,
title = "CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14",
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",
author = "Patterson, {Bruce K.} and Harish Seethamraju and Kush Dhody and Corley, {Michael J.} and Kazem Kazempour and Jay Lalezari and Pang, {Alina P.S.} and Christopher Sugai and Eisa Mahyari and Francisco, {Edgar B.} and Amruta Pise and Hallison Rodrigues and Wu, {Helen L.} and Webb, {Gabriela M.} and Park, {Byung S.} and Scott Kelly and Nader Pourhassan and Alina Lelic and Lama Kdouh and Monica Herrera and Eric Hall and Bimber, {Benjamin N.} and Matthew Plassmeyer and Raavi Gupta and Oral Alpan and O'Halloran, {Jane A.} and Mudd, {Philip A.} and Enver Akalin and Ndhlovu, {Lishomwa C.} and Sacha, {Jonah B.}",
note = "Funding Information: We gratefully acknowledge the patient participants and their caregivers Kristine Stryker, Victoria Caputo, Vagish Hemminge, Scott A Scheinin, Magdalena Mamczur-Madry, Sana Ahmed, Pamela Philllippsborn, Vagish Hemmige, Reena Joseph, and Jasmine Thallipllill who made this work possible. We acknowledge Lawrence Drew, Parviz Lalezari, Shaheed Abdulhaqq, Justin Greene, Whitney Weber, Jason Reed, Cleiton Pessoa, Katherine Bateman, and Jason Reed for critical reading of the manuscript. The WU-350 cohort was funded by a grant from the Barnes Jewish Hospital Foundationand by support from the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS)of the National Institutes of Health (NIH). This study was also supported partly by NIHR01 AI129703 toJBS. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Funding Information: We gratefully acknowledge the patient participants and their caregivers Kristine Stryker, Victoria Caputo, Vagish Hemminge, Scott A Scheinin, Magdalena Mamczur-Madry, Sana Ahmed, Pamela Philllippsborn, Vagish Hemmige, Reena Joseph, and Jasmine Thallipllill who made this work possible. We acknowledge Lawrence Drew, Parviz Lalezari, Shaheed Abdulhaqq, Justin Greene, Whitney Weber, Jason Reed, Cleiton Pessoa, Katherine Bateman, and Jason Reed for critical reading of the manuscript. The WU-350 cohort was funded by a grant from the B arnes Jewish Hospital Foundation and by support from the W ashington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the N ational Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). This study was also supported partly by NIH R01 AI129703 to JBS. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2021",
month = feb,
doi = "10.1016/j.ijid.2020.10.101",
language = "English",
volume = "103",
pages = "25--32",
journal = "International Journal of Infectious Diseases",
issn = "1201-9712",
}