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Another bit of evidence demonstrating the central

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Post# of 154677
(Total Views: 551)
Posted On: 02/11/2021 7:17:21 AM
Posted By: CTMedic
Another bit of evidence demonstrating the central role of CCR5 and monocyte activation in severe covid (reversed, of course, by the selective antagonism of CCR5 by leronlimab).

Bifurcated monocyte states are predictive of mortality in severe COVID-19
https://www.biorxiv.org/content/10.1101/2021.02.10.430499v1

Quote:
Critically ill patients admitted to the intensive care unit (ICU) manifested increased frequencies of inflammatory monocytes and plasmablasts that were also associated with ARDS not due to COVID-19. Single-cell RNAseq (scRNAseq)-based deconvolution of genomic states of peripheral immune cells revealed distinct gene modules that were associated with COVID-19 outcome. Notably, monocytes exhibited bifurcated genomic states, with expression of a cytokine gene module exemplified by CCL4 (MIP-1β) associated with survival and an interferon signaling module associated with death. These gene modules were correlated with higher levels of MIP-1β and CXCL10 levels in plasma, respectively. Monocytes expressing genes reflective of these divergent modules were also detectable in endotracheal aspirates. Machine learning algorithms identified the distinctive monocyte modules as part of a multivariate peripheral immune system state that was predictive of COVID-19 mortality. Follow-up analysis of the monocyte modules on ICU day 5 was consistent with bifurcated states that correlated with distinct inflammatory cytokines.



As a review, CCL4, in addition to CCL3 (MIP-1A), bind to CCR5 and are blocked by leronlimab.

https://investorshangout.com/post/view?id=6027461

https://breast-cancer-research.biomedcentral....21-01391-1

Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy

Quote:
Leronlimab blocks CCL5, CCL3, and CCL4 induced calcium signaling in breast cancer cells



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