Background: The SARS-CoV-2 virus underwent genetic alterations during viral genome replication, leading to the development of numerous variations including Alpha, Delta, Delta plus, Omicron, and other variants. The chemokine CXCL8 is known to directly restrict viral proteins by producing interferon as the antiviral efficacy. Subjects and methods: A total of137 nasal swabs and blood samples were collected from 89 positively corona virus infection disease-19 (COVID-19) patients and 48 healthy individuals. RNA was extracted and real-time reverse transcriptase polymerase chain reaction (rRT-PCR) was performed to variants detection by using special kits. CXCL8 levels were determined in Enzyme linked immune-sorbent assay (ELISA) assay. Results: Significant difference (p < /em> < 0.001) in the median levels of CXCL8 in patient higher than healthy control groups. Highest median of CXCL8 levels was shown with severe infection 308.6 (IQR: 66.6 – 783.5). Receiver-operating characteristic (ROC) analysis revealed that CXCL8 level was a good biomarker for immune response (Area under the curve (AUC) was 0.707). CXCL8 showed a significant difference with variants of SARS-CoV-2 (p < /em> < 0.001), where Delta/Delta plus variant patients had the highest median of CXCL8 level than other SARS-CoV-2 variant infections. Conclusion: Patients infected with Delta/Delta plus and Omicron had higher level of CXCL-8. CXCL-8 had positive relation with cardiac disease, renal failure, leukemia with COVID-19 infection.