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

HariOm Singh; Josna Wilson; Goldi Namdev; Meenakshi Bhattacharya; Anchal Singh; Supriya D Mahajan; Nemat Ali; Abdullah F AlAsmari

doi:10.1016/j.micpath.2025.107839

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

Microb Pathog. 2025 Jun 26:107839. doi: 10.1016/j.micpath.2025.107839. Online ahead of print.

Authors

HariOm Singh¹, Josna Wilson², Goldi Namdev², Meenakshi Bhattacharya³, Anchal Singh⁴, Supriya D Mahajan⁵, Nemat Ali⁶, Abdullah F AlAsmari⁶

Affiliations

¹ Department of Molecular Biology, National AIDS Research Institute, Pune, 411026, India. Electronic address: hsingh@nariindia.org.
² Department of Molecular Biology, National AIDS Research Institute, Pune, 411026, India.
³ Department of Medicine, Government Medical College & Hospital, University Road, Aurangabad, 431004, India.
⁴ Dept. of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005.
⁵ Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo's Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY14203, USA.
⁶ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

PMID: 40581269
DOI: 10.1016/j.micpath.2025.107839

Abstract

Background: 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.

Methods: 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.

Results: 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.

Keywords: CRP; Coronavirus disease of 2019; IL-8 Polymorphism; clinical outcomes; platelet counts; serum creatinine.