COVID-19 poses a serious risk, especially to the elderly. Additionally, COVID-19 has demonstrated a blatant sex-specific bias, with men exhibiting a more severe reaction and greater fatality rate. The aim of this study is to assess the genotypic and allelic frequencies of the chemokine ligand CXCL12 rs2839693 and its receptor CXCR4 rs2228014 according to age and sex. Also, to evaluate the interaction between age and sex and other risk variables affects how severe COVID-19 is.The present study conducted on 131 female and 169 male COVID-19 Egyptian patients who admitted to Assiut University Quarantine Hospital during the period from July to November 2022, the mean age of patients was 64.31±11.002 years old, patients with age > 65 years were 156 and < 65 years old were 144. Real-time PCR was used to identify the polymorphisms of CXCL12 rs2839693 and CXCR4 rs2228014 using a TaqMan test probe.No significant differences in CXCL12 rs2839693 and CXCR4 rs2228014 genotypic and allelic frequencies according to age and sex.Severe/critical illness was more prevalent in males than females. Also, severe and critical illness was more prevalent in patients with age >65years than patients with age ≤65.Of the statistics that are usually obtained upon admission, age and sex were significant indicators of the severity of the condition. Severe instances were more likely to occur in males and elders. Particular care needs to be paid to older male individuals, as well as individuals with comorbid diseases