Genetic variations in Interferon-Induced with Helicase C Domain 1: Impact on COVID-19 risk and severity in the Moroccan population

Background: The clinical spectrum of COVID-19 varies considerably, ranging from asymptomatic cases to severe disease and even death. This variability can partly be attributed to genetic differences in genes associated with inflammation and immune responses. Among these genes, Interferon Induced with Helicase C Domain 1 (IFIH1), which codes for a cytoplasmic sensor, plays a crucial role in detecting SARS-CoV-2 viral RNA and initiating the antiviral interferon (IFN) response, thereby constituting a key element of innate immune defense.

Aim: This study aims to examine the association between genetic variants in the IFIH1 gene and susceptibility to, as well as the severity of, COVID-19 in the Moroccan population.

Materials and methods: We conducted a case-control study involving 299 COVID-19 positive patients (149 severe, 150 benign) and 145 uninfected-SARS-CoV-2 controls. We determined the genotypes of two functional variants, rs1990760 (Ala946Thr) and rs3747517 (His843Arg), in the IFIH1 gene using predesigned TaqMan real-time allelic discrimination assay.

Results: Our results indicated that the TT genotype of rs1990760 was associated with increased susceptibility to SARS-CoV-2 under a recessive model (odds ratio [OR] = 2.22, 95 % confidence interval [CI] 1.28-3.84, P=0.003). Conversely, the CT genotype appeared to confer protection against SARS-CoV-2 infection (OR=0.58, 95 % CI 0.38-0.91, P=0.016) and COVID-19 severity (OR=0.56, 95 % CI 0.34-0.91, P=0.019). No significant association was found between rs3747517 and the risk of hospitalization or infection susceptibility.

Conclusion: These findings underscore the significance of genetic variability in the IFIH1 gene in shaping individual responses to SARS-CoV-2 in the Moroccan population.