CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14

•Anti-CCR5 humanized monoclonal antibody restored CD8 counts in COVID patients.•Inversely correlated with decreases in plasma viral load (pVL) by day 14.•CCL5/RANTES up 3–5-fold in mild/moderate patients and >100-fold in critical ones.•First report of highly sensitive, quantitative pVL by ddPCR i...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	International journal of infectious diseases Ročník 103; s. 25 - 32
Hlavní autori:	Patterson, Bruce K., Seethamraju, Harish, Dhody, Kush, Corley, Michael J., Kazempour, Kazem, Lalezari, Jay, Pang, Alina P.S., Sugai, Christopher, Mahyari, Eisa, Francisco, Edgar B., Pise, Amruta, Rodrigues, Hallison, Wu, Helen L., Webb, Gabriela M., Park, Byung S., Kelly, Scott, Pourhassan, Nader, Lelic, Alina, Kdouh, Lama, Herrera, Monica, Hall, Eric, Bimber, Benjamin N., Plassmeyer, Matthew, Gupta, Raavi, Alpan, Oral, O’Halloran, Jane A., Mudd, Philip A., Akalin, Enver, Ndhlovu, Lishomwa C., Sacha, Jonah B.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Canada Elsevier Ltd 01.02.2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases Elsevier
Predmet:	Adult Aged CCR5 CCR5 Receptor Antagonists - therapeutic use CD8-Positive T-Lymphocytes - immunology COVID-19 COVID-19 - immunology COVID-19 - virology COVID-19 Drug Treatment Cytokines - blood Female Humans Immunotherapy Leronlimab Male Middle Aged Plasma viral load RNA, Viral - blood SARS-CoV-2 Time Factors COVID-19 Plasma viral load CCR5 Immunotherapy Leronlimab
ISSN:	1201-9712, 1878-3511, 1878-3511
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	•Anti-CCR5 humanized monoclonal antibody restored CD8 counts in COVID patients.•Inversely correlated with decreases in plasma viral load (pVL) by day 14.•CCL5/RANTES up 3–5-fold in mild/moderate patients and >100-fold in critical ones.•First report of highly sensitive, quantitative pVL by ddPCR in COVID patients.•Statistically significant drop in IL-6 by day 14 of treatment. 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 severe COVID-19 patients. In March 2020, 10 terminally ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication. We analyzed changes in clinical presentation, immune cell populations, inflammation, as well as SARS-CoV-2 plasma viremia before and 14 days after treatment. Over the 14-day study period, six patients survived, two were extubated, and one discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared with the baseline, we observed a concomitant statistically significant reduction in plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL). Furthermore, the increase in the CD8 percentage was inversely correlated with the reduction in pVL (r = −0.77, p = 0.0013). Our study design precludes clinical efficacy inferences but the results implicate CCR5 as a therapeutic target for COVID-19 and they form the basis for ongoing randomized clinical trials.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Co-senior authors.
ISSN:	1201-9712 1878-3511 1878-3511
DOI:	10.1016/j.ijid.2020.10.101