Genetic Variability of IFNAR2 Gene and Risk of COVID-19 Critical Illness Among the Tunisian Population

The IFNAR2 gene encodes an essential component of the type I interferon receptor, which is essential for antiviral defense. It has been proven that the severity of COVID-19 may be influenced by the genetic variants in IFNAR2; however, the results are inconclusive in the African cohorts. Thus, in this study, we investigate the association between three IFNAR2 SNPs and the critical form of COVID-19 in the Tunisian population. A total of 413 COVID-19 patients classified as hospitalized with critical illness (ICU) (n = 46) and non-hospitalized (n = 367) are included. Genotyping of three IFNAR2 polymorphisms (rs1051393, rs2236757, rs9984273) was performed using Taq Man RT-PCR assays. rs2236757 (OR = 0.31, 95% CI: 0.16–0.60), p = 4 × 10−4) and rs9984273 (OR = 0.41, 95% CI: 0.22–0.76, p = 0.0055) were associated with COVID-19 severity with a potential protective effect. However, rs1051393 did not show a significant association with disease severity. Additionally, exploratory haplotype analysis suggested a possible protective association for the TAC haplotype (OR = 0.11, 95% CI: 0.02–0.86, p = 0.036), based on a very small number of carriers and not significant after correction for multiple testing. The GAC haplotype, absent from ICU patients, yielded a continuity-corrected OR of 0.03 (95% CI [0.002–0.53]); this estimate rests on a zero cell and is hypothesis-generating only. These preliminary findings, obtained from a single-center cohort with a limited number of critically ill patients, warrant replication in larger, independent, and multicentric populations.