Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33186704&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14 #MMPMID33186704
Patterson BK; Seethamraju H; Dhody K; Corley MJ; Kazempour K; Lalezari J; Pang APS; Sugai C; Mahyari E; Francisco EB; Pise A; Rodrigues H; Wu HL; Webb GM; Park BS; Kelly S; Pourhassan N; Lelic A; Kdouh L; Herrera M; Hall E; Bimber BN; Plassmeyer M; Gupta R; Alpan O; O'Halloran JA; Mudd PA; Akalin E; Ndhlovu LC; Sacha JB
Int J Infect Dis 2021[Feb]; 103 (?): 25-32 PMID33186704show ga
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 severe COVID-19 patients. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
free
free
free
Int+J+Infect+Dis 2021 ; 103 (?): 25-32
