1. Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity
- Author
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Helena Gil-Peña, Francisco J. Jimeno-Demuth, Elena Domínguez-Garrido, Sergio Pérez-Oliveira, Victoria Alvarez, Marta García-Clemente, Inés López-Alonso, Guillermo M. Albaiceta, José Gutiérrez-Rodríguez, Cristina Hernández-González, Juan Gómez, Ana I. Enriquez, Beatriz Suarez-Alvarez, Carlos López-Larrea, Tamara Hermida, Elías Cuesta-Llavona, Salvador Tranche, Laura Amado-Rodríguez, and Eliecer Coto
- Subjects
Male ,0301 basic medicine ,Receptors, CCR5 ,Chemokine receptor CCR5 ,Short Communication ,SARS-Cov-2 ,viruses ,Immunology ,Risk Assessment ,Severity of Illness Index ,03 medical and health sciences ,Patient Admission ,0302 clinical medicine ,Risk Factors ,Severity of illness ,Genetic variation ,Genetic susceptibility ,Genetic predisposition ,Humans ,Immunology and Allergy ,Medicine ,Genetic Predisposition to Disease ,Aged ,Aged, 80 and over ,Pharmacology ,biology ,business.industry ,Case-control study ,Genetic Variation ,COVID-19 ,virus diseases ,Middle Aged ,Phenotype ,CCR5 delta32 ,Gene expression profiling ,Intensive Care Units ,030104 developmental biology ,Genetic marker ,Case-Control Studies ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,biology.protein ,Female ,business - 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.
- Published
- 2021