Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19
Bruce K Patterson, Harish Seethamraju, Kush Dhody, Michael J Corley, Kazemm Kazempour, Jay P Lalezari, Alina PS Pang, Christopher Sugai, Edgar B Francisco, Amruta Pise, Hallison Rodrigues, Matthew Ryou, Helen L Wu, Gabriela M Webb, Byung S Park, Scott Kelly, Nadar Pourhassan , Alena Lelic, Lama Kdouh, Monica Herrera, Eric Hall, Enver Aklin, View ORCID ProfileLishomwa Ndhlovu, Jonah B Sacha
https://www.medrxiv.org/content/10.1101/2020....20084673v1
Nader Pourhassan is a coauthor on Bruce Pattersons paper. Blocking your own paper? Ridiculous, utter nonsense.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is now pandemic with nearly three million cases reported to date. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Emerging results indicate a dysregulated immune response characterized by runaway inflammation, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-19. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation in severe disease caused by SARS-CoV-2 infection are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Following compassionate care treatment with the CCR5 blocking antibody leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. Consistent with reduction of plasma IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.
https://www.cytodyn.com/investors/news-events...b-disrupts
A direct quote taken from the PR link above:
Nader clearly credits Bruce Patterson, and has always respected Bruce Patterson.
Bruce K Patterson, Harish Seethamraju, Kush Dhody, Michael J Corley, Kazemm Kazempour, Jay P Lalezari, Alina PS Pang, Christopher Sugai, Edgar B Francisco, Amruta Pise, Hallison Rodrigues, Matthew Ryou, Helen L Wu, Gabriela M Webb, Byung S Park, Scott Kelly, Nadar Pourhassan , Alena Lelic, Lama Kdouh, Monica Herrera, Eric Hall, Enver Aklin, View ORCID ProfileLishomwa Ndhlovu, Jonah B Sacha
https://www.medrxiv.org/content/10.1101/2020....20084673v1
Nader Pourhassan is a coauthor on Bruce Pattersons paper. Blocking your own paper? Ridiculous, utter nonsense.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is now pandemic with nearly three million cases reported to date. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Emerging results indicate a dysregulated immune response characterized by runaway inflammation, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-19. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation in severe disease caused by SARS-CoV-2 infection are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Following compassionate care treatment with the CCR5 blocking antibody leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. Consistent with reduction of plasma IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.
https://www.cytodyn.com/investors/news-events...b-disrupts
A direct quote taken from the PR link above:
Quote:Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn said, “We are now most hopeful the entire medical community will understand the potential benefit leronlimab can provide critically ill COVID-19 patients. Moreover, this discovery by Dr. Bruce Patterson that leronlimab decreases plasma viral load may have tremendous long-term positive ramifications to bring this pandemic under control. We are grateful that we are able to release this research at such a critical time for patients throughout the world.”
Nader clearly credits Bruce Patterson, and has always respected Bruce Patterson.
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