This is the way I control my COD (hope reading alo
Post# of 154850
(Total Views: 637)
Posted On: 02/10/2021 8:20:58 AM
This is the way I control my COD (hope reading along helps all of you the same way it always helps me 
), from Dr. Patterson's et-al paper:
Discussion
In this study, we investigated the involvement of the chemokine receptor CCR5 in COVID-19 and obtained data from 10 critically ill patients with severe COVID-19 that demonstrated reductions in inflammation, restoration of T cell lymphocytopenia, and reduced SARS-CoV-2 plasma viremia following leronlimab-mediated CCR5 blockade. We found statistically significant increases in IL-1β, IL-6, IL-8, and RANTES in these critically ill patients compared with healthy controls.
The increases in these cytokines are the hallmark of COVID-19 and elevation of the chemokine CCL5/RANTES has been demonstrated across the COVID-19 disease spectrum from mild (Zhao et al., 2020) to severe (Li et al., 2020) patients.
RANTES was elevated to a greater extent than the other CCR5 binding chemokines MIP-1α and MIP-1β, probably due to the production of RANTES in respiratory epithelial cells (in addition to immune cells) in respiratory viral infections (Schroth et al., 1999).
We also found a profound reduction in the CD8 percentage with concomitant increases in the CD4/CD8 ratio. In this cohort of critical COVID-19 patients, SARS-CoV-2 RNA was detectable and quantifiable in plasma samples from all patients.
For the first time, we demonstrated that restoration of the CD8 T-cell numbers was significantly correlated with decreases in the plasma viral load.
Overall, our results showed that therapy with a CCR5 antagonist could reduce the cytokine storm, resolve the profound CD-8 T-cell lymphopenia, and reduce the plasma viral load to undetectable levels by day 14. These data support recent studies that suggested the potential for targeting CCR5 as a therapeutic in COVID-19 (Chua et al., 2020).
Recent studies showed that a significant number of COVID-19 patients had increased risks of strokes, blood clots, and other thromboembolic events (Grillet et al., 2020). Platelet activation leads to initiation of the coagulation cascade and it can be triggered by chemokines including CCL5/RANTES (Machlus et al., 2016), thereby suggesting that leronlimab treatment may be beneficial beyond its immunomodulatory effects on inflammation and hemostasis in COVID-19 patients.
Given medical triage resulting in patient death and the lack of a placebo control group, we cannot comment on the impact of leronlimab on the clinical outcomes in these patients. Anecdotal evidence has been reported of clinical improvements in COVID-19 patients following leronlimab treatment (Mottet, 2020), but randomized controlled trials are required to determine the efficacy of leronlimab in COVID-19. Indeed, randomized, double blind, placebo controlled clinical trials are underway to assess the efficacy of leronlimab treatments in patients with mild to moderate (NCT04343651) (ClinicalTrials.gov, 2020) and severe to critical (NCT04347239) COVID-19 (ClinicalTrials.gov).
In summary, our results suggest the involvement of CCR5 in the pathology of SARS-CoV-2, and that inhibiting the activity of CCL5 via CCR5/RANTES blockade represents a novel therapeutic strategy for COVID-19 with both immunological and virological implications.
), from Dr. Patterson's et-al paper: Discussion
In this study, we investigated the involvement of the chemokine receptor CCR5 in COVID-19 and obtained data from 10 critically ill patients with severe COVID-19 that demonstrated reductions in inflammation, restoration of T cell lymphocytopenia, and reduced SARS-CoV-2 plasma viremia following leronlimab-mediated CCR5 blockade. We found statistically significant increases in IL-1β, IL-6, IL-8, and RANTES in these critically ill patients compared with healthy controls.
The increases in these cytokines are the hallmark of COVID-19 and elevation of the chemokine CCL5/RANTES has been demonstrated across the COVID-19 disease spectrum from mild (Zhao et al., 2020) to severe (Li et al., 2020) patients.
RANTES was elevated to a greater extent than the other CCR5 binding chemokines MIP-1α and MIP-1β, probably due to the production of RANTES in respiratory epithelial cells (in addition to immune cells) in respiratory viral infections (Schroth et al., 1999).
We also found a profound reduction in the CD8 percentage with concomitant increases in the CD4/CD8 ratio. In this cohort of critical COVID-19 patients, SARS-CoV-2 RNA was detectable and quantifiable in plasma samples from all patients.
For the first time, we demonstrated that restoration of the CD8 T-cell numbers was significantly correlated with decreases in the plasma viral load.
Overall, our results showed that therapy with a CCR5 antagonist could reduce the cytokine storm, resolve the profound CD-8 T-cell lymphopenia, and reduce the plasma viral load to undetectable levels by day 14. These data support recent studies that suggested the potential for targeting CCR5 as a therapeutic in COVID-19 (Chua et al., 2020).
Recent studies showed that a significant number of COVID-19 patients had increased risks of strokes, blood clots, and other thromboembolic events (Grillet et al., 2020). Platelet activation leads to initiation of the coagulation cascade and it can be triggered by chemokines including CCL5/RANTES (Machlus et al., 2016), thereby suggesting that leronlimab treatment may be beneficial beyond its immunomodulatory effects on inflammation and hemostasis in COVID-19 patients.
Given medical triage resulting in patient death and the lack of a placebo control group, we cannot comment on the impact of leronlimab on the clinical outcomes in these patients. Anecdotal evidence has been reported of clinical improvements in COVID-19 patients following leronlimab treatment (Mottet, 2020), but randomized controlled trials are required to determine the efficacy of leronlimab in COVID-19. Indeed, randomized, double blind, placebo controlled clinical trials are underway to assess the efficacy of leronlimab treatments in patients with mild to moderate (NCT04343651) (ClinicalTrials.gov, 2020) and severe to critical (NCT04347239) COVID-19 (ClinicalTrials.gov).
In summary, our results suggest the involvement of CCR5 in the pathology of SARS-CoV-2, and that inhibiting the activity of CCL5 via CCR5/RANTES blockade represents a novel therapeutic strategy for COVID-19 with both immunological and virological implications.
(12)
(0)