The CCR5-delta32 variant might explain part of the association between COVID-19 and the chemokine-receptor gene cluster

Abstract

AbstractA polymorphism in the LZTFL1 gene located in the chemokine-receptor gene cluster (chromosome 3p) has been associated with the risk of developing COVID-19. The chemokine receptor-5 (CCR5) maps to this region, and the common 32 bp deletion variant (Δ32) has been associated with the extent of inflammatory disease and the outcome in several viral diseases. Several studies have also suggested that the pharmacological targeting of CCR5 could reduce the impact of SARS-CoV-2 infection and the severity of COVID-19. We sought to investigate whether this polymorphism was associated with the risk of moderate-severe COVID-19.We genotyped 294 patients who required hospitalization due to COVID-19 (85 were severe cases) and 460 controls. We found a significantly lower frequency of CCR5-Δ32 among the COVID-19 patients (0.10 vs 0.18 in controls; p=0.002, OR=0.48, 95%CI=0.29-0.76). The difference was mainly due to the reduced frequency of CCR5-Δ32 carriers in the severe, significantly lower than in the non-severe patients (p=0.036). Of note, we did not find deletion-homozygotes among the patients compared to 1% among controls. We also confirmed the association between a LZTFL1 variant and COVID-19. Our study points to CCR5 as a promising target for treatment of COVID-19, but requires validation in additional large cohorts. In confirmed by others, the genetic analysis of CCR5-variants (such as Δ32) might help to identify patients with a higher susceptibility to severe COVID-19.