Abstract
Genome-wide association studies have recently identified 3p21.31, with lead variant pointing to the CXCR6 gene, as the strongest thus far reported susceptibility risk locus for severe manifestation of COVID-19. In order the determine its role, we measured plasma levels of Chemokine (C-X-C motif) ligand 16 (CXCL16) in the plasma of COVID-19 hospitalized patients. CXCL16 interacts with CXCR6 promoting chemotaxis or cell adhesion. The CXCR6/CXCL16 axis mediates homing of T cells to the lungs in disease and hyper-expression is associated with localised cellular injury. To characterize the CXCR6/CXCL16 axis in the pathogenesis of severe COVID-19, plasma concentrations of CXCL16 collected at baseline from 115 hospitalized COVID-19 patients participating in ODYSSEY COVID-19 clinical trial were assessed together with a set of controls. We report elevated levels of CXCL16 in a cohort of COVID-19 hospitalized patients. Specifically, we report significant elevation of CXCL16 plasma levels in association with severity of COVID-19 (as defined by WHO scale) (P-value < 0.02). Our current study is the largest thus far study reporting CXCL16 levels in COVID-19 hospitalized patients (with whole-genome sequencing data available). The results further support the significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19 and warrants further studies to understand which patients would benefit most from targeted treatments.
Keywords: COVID-19; CXCL16; CXCR6; Lung infection; Whole genome sequencing.
【저자키워드】 COVID-19, Lung infection, whole genome sequencing., CXCL16, CXCR6, 【초록키워드】 whole-genome sequencing, clinical trial, Pathogenesis, severe COVID-19, T cells, susceptibility, variant, lung, risk, Lung infection, hospitalized patients, Cohort, T cell, Whole genome sequencing, severity of COVID-19, Lungs, Immunopathogenesis, Genome-wide association studies, Patient, plasma, WHO, disease, association, hospitalized COVID-19 patient, cellular, Ligand, Injury, Plasma levels, CXCL16, CXCR6, Support, plasma concentration, P-value, locus, plasma concentrations, chemotaxis, motif, controls, benefit, Cell, homing, defined, collected, reported, elevated, determine, hospitalized patient, interact, baseline, were assessed, 【제목키워드】 severe COVID-19 patient,