Association of TLR4 Gene Polymorphism (rs4986790) of SARS-CoV-2 Patients with Cognitive Impairment

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which gave rise to coronavirus infectious disease (COVID-19) in late 2019 as a respiratory illness, has significantly impacted global health and society. Recently, there has been a link between SARS-CoV-2 and Toll-like receptor4 (TLR4). Thus, the current study aimed to shed light on how TLR4 single-nucleotide polymorphism (SNP) (rs4986790) possibly link to the severity of disease in Iraqi COVID-19 patients and establish their role in recovered individuals with cognitive impairment. A case-control study (60 patients, 30 recovered and 50 controls) investigates the A/G genotype of rs4986790 in all studied groups, using a conventional polymerase chain reaction with an allele-specific primer method. Results showed a significant increase in the median age accompanied by severe cases (p =0.003) and more than 50% of the moderate infections in the youth category. Regarding the recovered individual’s occurrence six cases along with ages median of 49.5 (45.8-57) males and females with a history of mild to moderate infection. In clinical severity, allele and genotype frequencies of A/G rs4986790 TLR4 polymorphism showed no significant difference between COVID-19 patients’ group (OR = 0.58; 95% CI = 0.28–1.20; p = 0.200). In recovered individuals with cognitive impairment, despite 50% cognitive impairment in the AG genotype, there is no significant difference compared to intact recovered individuals (OR = 2.62; 95% CI = 0.39– 17.78; p = 0.370). On the other hand, there were statistically significant variations (p < 0.001) in the concentrations of ferritin, D. dimer, and LDH. These inflammatory markers demonstrate their major role in COVID-19 illness and its harshness and aggravation. They were significantly greater in severe-critical cases but returned to normal in the recovered groups. In conclusion, recovered individuals with cognitive impairment are significantly associated with age older. On the other hand, despite 50% cognitive impairment in the AG rs4986790 genotype, there are no statistically significant differences between cognitive impairment and studied TLR4 SNPs. A/G rs4986790 of TLR4 required more information to explore their role in cognitive impairment and infection severity.