Potential protective association of the AA genotype and a allele of CXCR4 rs2228014 polymorphism with COVID-19 severity in adult egyptians

By the end of December 2019, a new coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, and the cause of the disease was named coronavirus disease 2019 (COVID-19). Several genetic factors have been implicated in diverse responses to SARS-CoV-2 infection, such as the C-X-C chemokine receptor 4 (CXCR4) rs2228014 polymorphism, which has been previously studied in various diseases but has not been explored in the context of COVID-19 severity. The current study aimed to assess the association between the rs2228014 polymorphism in the CXCR4 gene and the severity of COVID-19, which has not been previously reported. This cross-sectional study analyzed 300 adult Egyptian COVID-19 patients (156 with mild or moderate and 144 with severe or critical symptoms) admitted to Assiut University Quarantine Hospital from June to September 2022 during the omicron variant. The rs2228014 polymorphism in the CXCR4 gene was detected using real-time PCR with a TaqMan assay probe. Receiver operating characteristic (ROC) curve analysis was used to determine the best cutoff values for C-reactive protein (CRP) that can be used to estimate the severity of COVID-19. P values less than 0.05 were considered to indicate statistical significance. No significant differences in the allelic or genotypic frequencies of CXCR4 rs2228014 were detected between the severity groups. However, the exclusive presence of the AA genotype in mild or moderate cases suggests its potential protective role. Additionally, significant differences in myalgia presentation, leukocyte counts and antibiotic use, were observed among different genotypes. Statistical data showed that the severity of COVID-19 could be predicted at a cutoff value of CRP > 30 mg/L, with a sensitivity of 74.3% and a specificity of 42.9%. The present findings suggest a potential protective role of the AA genotype and A allele of CXCR4 rs2228014 against severe COVID-19. Additionally, factors such as lack of vaccination and comorbidities such as hypertension, renal disease, and diabetes mellitus were associated with increased disease severity.