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Posted On: 01/13/2021 3:35:56 PM
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Chemokine receptor gene polymorphisms and COVID-19: Could knowledge gained from HIV/AIDS be important?
2.3. CCR5 as a therapeutic target for COVID-19
A study by Patterson et al (Patterson et al., 2020) has reported profound elevation of plasma IL-6 and CCL5 (also known as RANTES), a ligand for CCR5, decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia in 10 terminally-ill, critical COVID-19 patients. Following treatment with the CCR5-blocking antibody leronlimab, the authors 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 transcriptomics showed that there were declines in myeloid cell clusters expressing IL-6 and interferon-related genes. The authors state, “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.”
According to the authors, leronlimab does not downregulate CCR5 surface expression or deplete CCR5-expressing cells, but does prevent CCL5-induced calcium mobilization in CCR5+ cells. This ability to specifically prevent CCL5-induced activation and chemotaxis of inflammatory CCR5+ macrophages and T cells suggests how leronlimab-mediated CCR5 blockade may be effective in resolving the hyperinflammatory state in COVID-19 and restoring more effective anti-viral immunity (Patterson et al., 2020).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448762/
2.3. CCR5 as a therapeutic target for COVID-19
A study by Patterson et al (Patterson et al., 2020) has reported profound elevation of plasma IL-6 and CCL5 (also known as RANTES), a ligand for CCR5, decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia in 10 terminally-ill, critical COVID-19 patients. Following treatment with the CCR5-blocking antibody leronlimab, the authors 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 transcriptomics showed that there were declines in myeloid cell clusters expressing IL-6 and interferon-related genes. The authors state, “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.”
According to the authors, leronlimab does not downregulate CCR5 surface expression or deplete CCR5-expressing cells, but does prevent CCL5-induced calcium mobilization in CCR5+ cells. This ability to specifically prevent CCL5-induced activation and chemotaxis of inflammatory CCR5+ macrophages and T cells suggests how leronlimab-mediated CCR5 blockade may be effective in resolving the hyperinflammatory state in COVID-19 and restoring more effective anti-viral immunity (Patterson et al., 2020).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448762/
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