Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity

Abstract

The chemokine receptor CCR5 has been implicated in COVID-19. CCR5 and its ligands are overexpressed in patients. The pharmacological targeting of CCR5 would improve the COVID-19 severity. We sought to investigate the role of the CCR5-Δ32 variant (rs333) in COVID-19. The CCR5 -Δ32 was genotyped in 801 patients (353 in the intensive care unit, ICU) and 660 healthy controls, and the deletion was significantly less frequent in hospitalysed COVID-19 than in healthy controls (p=0.01, OR=0.66 , 95%CI=0.49-0.88). Of note, we did not find homozygotes among the patients, compared to 1% of the controls. The CCR5 transcript was measured in leukocytes from 85 patients and 40 controls. We found a significantly higher expression of the CCR5 transcript among the patients, with significant difference when comparing the non-deletion carriers (controls=35; patients=n=81; p=0.01). ICU-patients showed non-significantly higher expression than no-ICU cases. Our study points to CCR5 as a genetic marker for COVID-19. The pharmacological targeting of CCR5 should be a promising treatment for COVID-19.

Unraveling Risk Genes of COVID-19 by Multi-Omics Integrative Analyses

“…It is of interest that anti-CCR5 antibody leronlimab has been tried as a post-COVID-19 therapeutic molecule and shown to downregulate both inflammatory cytokine profile and the copy number of SARS-CoV2 RNA (22). In a recent study, the CCR5-32 variant was found to be significantly less frequent in hospitalized COVID-19 than in healthy controls (P = 0.01, OR = 0.66, 95% CI = 0.49-0.88), with no homozygotes found among the patients, compared to 1% of the controls (23). In addition, CCR5 transcript was expressed among the patients at significantly higher levels than in the healthy non-deletion carriers (P = 0.01).…”

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

“…Last but not least, nowadays, the role of co-receptor 5 (CCR5) deletion 32 in coronavirus susceptibility is still controversial [77][78][79][80].…”

Rationale of using the dual chemokine receptor CCR2/CCR5 inhibitor cenicriviroc for the treatment of COVID-19

“…Functional blockade of CCR5 by maraviroc and CCR2 by clinical candidate agents to date has met with a fairly benign safety profile in patients across a range of indications. The homozygous Δ32 mutation of CCR5 has been reported as less prevalent in COVID-19 patients, with transcript levels higher in patients versus controls [103,104], although disease course has been reported with no association [105]. However, of particular note is the strong association of the Δ32 CCR5 genotype with increased susceptibility to West Nile virus infection [106,107].…”