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. 2021 Sep:98:107825.
doi: 10.1016/j.intimp.2021.107825. Epub 2021 Jun 2.

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

Elías Cuesta-Llavona  1 , Juan Gómez  1 , Guillermo M Albaiceta  2 , Laura Amado-Rodríguez  2 , Marta García-Clemente  3 , José Gutiérrez-Rodríguez  4 , Inés López-Alonso  5 , Tamara Hermida  6 , Ana I Enríquez  6 , Cristina Hernández-González  6 , Helena Gil-Peña  1 , Elena Domínguez-Garrido  7 , Sergio Pérez-Oliveira  8 , Victoria Alvarez  1 , Carlos López-Larrea  9 , Beatriz Suarez-Alvarez  10 , Salvador Tranche  11 , Francisco J Jimeno-Demuth  12 , Eliecer Coto  13
Affiliations

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

Elías Cuesta-Llavona et al. Int Immunopharmacol. 2021 Sep.

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 = 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.

Keywords: CCR5 delta32; COVID-19; Genetic susceptibility; SARS-Cov-2.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Expression rate of CCR5 cDNA in total leukocytes, relative to the normalizing gene (ACTB). Patients and matched controls. The box-plots corresponded to Wt/Wt homozygotes, and the stars indicate values for the CCR5 Δ32 heterozygotes (5 controls and 4 patients). Lower CCR5/ACTB cycle threshold (Ct) ratios indicate higher CCR5-transcript levels.
See this image and copyright information in PMC

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