tetano
Editor, Senior Moderator
Int J Infect Dis
. 2020 Nov 10;S1201-9712(20)32305-5.
doi: 10.1016/j.ijid.2020.10.101. Online ahead of print.
CCR5 Inhibition in Critical COVID-19 Patients Decreases Inflammatory Cytokines, Increases CD8 T-Cells, and Decreases SARS-CoV2 RNA in Plasma by Day 14
Bruce K Patterson[SUP] 1 [/SUP], Harish Seethamraju[SUP] 2 [/SUP], Kush Dhody[SUP] 3 [/SUP], Michael J Corley[SUP] 4 [/SUP], Kazem Kazempour[SUP] 3 [/SUP], Jay Lalezari[SUP] 5 [/SUP], Alina P S Pang[SUP] 4 [/SUP], Christopher Sugai[SUP] 6 [/SUP], Eisa Mahyari[SUP] 7 [/SUP], Edgar B Francisco[SUP] 8 [/SUP], Amruta Pise[SUP] 8 [/SUP], Hallison Rodrigues[SUP] 8 [/SUP], Helen L Wu[SUP] 7 [/SUP], Gabriela M Webb[SUP] 7 [/SUP], Byung S Park[SUP] 7 [/SUP], Scott Kelly[SUP] 9 [/SUP], Nader Pourhassan[SUP] 9 [/SUP], Alina Lelic[SUP] 10 [/SUP], Lama Kdouh[SUP] 10 [/SUP], Monica Herrera[SUP] 11 [/SUP], Eric Hall[SUP] 11 [/SUP], Benjamin N Bimber[SUP] 7 [/SUP], Matthew Plassmeyer[SUP] 12 [/SUP], Raavi Gupta[SUP] 13 [/SUP], Oral Alpan[SUP] 12 [/SUP], Jane A O'Halloran[SUP] 14 [/SUP], Philip A Mudd[SUP] 15 [/SUP], Enver Akalin[SUP] 2 [/SUP], Lishomwa C Ndhlovu[SUP] 4 [/SUP], Jonah B Sacha[SUP] 7 [/SUP]
Affiliations
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 patients with severe COVID-19 disease.
Methods: In March 2020, ten terminally-ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication (EIND). 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 6/10 patients survived, 2 extubated, and 1 patient was discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared to baseline, we observed a concomitant statistically significant reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL) compared to controls. Further, the increase in CD8% was inversely correlated with reduction in pVL (r = -0.77, p = 0.0013).
Conclusions: While the current study design precludes clinical efficacy inferences, these results implicate CCR5 as a therapeutic target for COVID-19 and form the basis for ongoing randomized clinical trials.
Keywords: CCR5; COVID-19; immunotherapy; leronlimab; plasma viral load.
. 2020 Nov 10;S1201-9712(20)32305-5.
doi: 10.1016/j.ijid.2020.10.101. Online ahead of print.
CCR5 Inhibition in Critical COVID-19 Patients Decreases Inflammatory Cytokines, Increases CD8 T-Cells, and Decreases SARS-CoV2 RNA in Plasma by Day 14
Bruce K Patterson[SUP] 1 [/SUP], Harish Seethamraju[SUP] 2 [/SUP], Kush Dhody[SUP] 3 [/SUP], Michael J Corley[SUP] 4 [/SUP], Kazem Kazempour[SUP] 3 [/SUP], Jay Lalezari[SUP] 5 [/SUP], Alina P S Pang[SUP] 4 [/SUP], Christopher Sugai[SUP] 6 [/SUP], Eisa Mahyari[SUP] 7 [/SUP], Edgar B Francisco[SUP] 8 [/SUP], Amruta Pise[SUP] 8 [/SUP], Hallison Rodrigues[SUP] 8 [/SUP], Helen L Wu[SUP] 7 [/SUP], Gabriela M Webb[SUP] 7 [/SUP], Byung S Park[SUP] 7 [/SUP], Scott Kelly[SUP] 9 [/SUP], Nader Pourhassan[SUP] 9 [/SUP], Alina Lelic[SUP] 10 [/SUP], Lama Kdouh[SUP] 10 [/SUP], Monica Herrera[SUP] 11 [/SUP], Eric Hall[SUP] 11 [/SUP], Benjamin N Bimber[SUP] 7 [/SUP], Matthew Plassmeyer[SUP] 12 [/SUP], Raavi Gupta[SUP] 13 [/SUP], Oral Alpan[SUP] 12 [/SUP], Jane A O'Halloran[SUP] 14 [/SUP], Philip A Mudd[SUP] 15 [/SUP], Enver Akalin[SUP] 2 [/SUP], Lishomwa C Ndhlovu[SUP] 4 [/SUP], Jonah B Sacha[SUP] 7 [/SUP]
Affiliations
- PMID: 33186704
- PMCID: PMC7654230
- DOI: 10.1016/j.ijid.2020.10.101
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 patients with severe COVID-19 disease.
Methods: In March 2020, ten terminally-ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication (EIND). 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 6/10 patients survived, 2 extubated, and 1 patient was discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared to baseline, we observed a concomitant statistically significant reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL) compared to controls. Further, the increase in CD8% was inversely correlated with reduction in pVL (r = -0.77, p = 0.0013).
Conclusions: While the current study design precludes clinical efficacy inferences, these results implicate CCR5 as a therapeutic target for COVID-19 and form the basis for ongoing randomized clinical trials.
Keywords: CCR5; COVID-19; immunotherapy; leronlimab; plasma viral load.