IL-8 polymorphisms (-251T/A, -1633T/C) and their effects on COVID-19 clinical outcomes: An observational study.

Publication date: Jun 26, 2025

COVID-19 presents with a wide spectrum of clinical outcomes, ranging from asymptomatic infection to critical illness. The cytokine storm is a hallmark of severe COVID-19 and is associated with elevated levels of pro-inflammatory cytokines, often observed in severe cases. Genetic polymorphisms in the IL-8 gene may influence individual responses to SARS-CoV-2 infection and the severity of the disease. A case-control study was conducted involving 200 COVID-19 patients and 201 healthy controls. Two IL-8 gene polymorphisms, -251T/A and +1633T/C, were genotyped using the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique. The IL-8 -251TA genotype and -251A allele were significantly associated with COVID-19 patients (P=0. 02, OR=2. 31; P=0. 03, OR=1. 38). The AT haplotype (-251A/+1633C) showed a non-significant trend toward increased risk for COVID-19 (P=0. 11, OR=2. 24). The IL-8 +1633TT genotype was associated with impaired platelet counts among COVID-19 patients (P=0. 05, OR=2. 42). The IL-8 -251TA genotype was significantly associated with all stages of COVID-19 severity-critical (P=0. 05, OR=8. 15), severe (P=0. 002, OR=2. 74), moderate (P=0. 008, OR=2. 16), and mild (P=0. 01, OR=2. 89). In contrast, the IL-8 -251AA genotype was significantly associated with the critical stage (P=0. 04, OR=2. 53). A marginally significant association was observed between the IL-8 +1633CT genotype and the severe stage of COVID-19 (P=0. 07, OR=2. 13). Additionally, a borderline significant association was noted between elevated serum creatinine levels and the IL-8 -251AA genotype (P=0. 07, OR=2. 45). In conclusion, the IL-8 -251T/A polymorphism may serve as a potential risk factor for severe disease progression; the +1633TT genotype may be linked to thrombocytopenia and poor clinical outcomes; and the -251AA genotype may be associated with elevated serum creatinine levels and an increased risk of renal dysfunction.

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