CXCL12/CXCR4 as a potential axis in diagnosis and predicting disease severity in COVID-19 patients: a new perspective

Abstract

Coronavirus disease 2019 (COVID-19) exhibits variations in terms of patients’ clinical symptoms and levels of routinely employed biochemical markers. The aim of the current study was to determine the correlation between serum levels of the C-X-C chemokine ligand type 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4), one of its specific receptors, and disease severity in COVID-19 patients. Sixty-nine patients were diagnosed with COVID-19 from February to July 2021, and a healthy control group of 39 individuals were enrolled in the study. Patients were divided into subgroups: mild-moderate and severe. Serum CXCL12 and CXCR4 levels were measured using the enzyme-linked immunosorbent assay method. CXCL12 and CXCR4 concentrations were both significantly higher in the clinically severe disease group compared to the mild-moderate disease group (p<0.05 in both groups). CXCL12 and CXCR4 levels were also significantly higher in the patients with clinically mild-moderate disease compared to the control group (p<0.001 and p<0.05, respectively). Both CXCL12 and CXCR4 levels were correlated with clinical severity. Serum CXCL12 and CXCR4 levels were significantly positively correlated. Assuming a cut-off value of 1.44 ng/mL, serum CXCL12 levels showed 98 % sensitivity and 84 % specificity to distinguish between COVID-19 patients and healthy individuals (AUC=0.98, p<0.001, 95 % CI=0.95–1.0). Serum CXCR4 levels distinguished individuals with COVID-19 from healthy controls with 88 % sensitivity and 72 % specificity at a cut-off value of 69.7 pg/mL (AUC=0.82, p<0.001, 95 % CI=0.74–0.9). Serum CXCL12 and CXCR4 levels may be included among the biomarkers used to differentiate patients with COVID-19 and determine the clinical severity of the disease.