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Introduction: The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results: The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784-52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673-81.249), both p < 0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p < 0.001). Conclusion: ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.
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BACKGROUND: Type 1 diabetes mellitus is described as a chronic metabolic disorder characterized by aggressive immune β-cell destruction. There are a number of varied immune mechanisms for sustaining self-tolerance in opposition to the autoimmune disorders. A recessive tolerance is accomplished by thymic gland via a negative assortment of different clones, while a dominant tolerance is accomplished by the regulatory T cells (Treg) in the periphery. Treg (CD4+ CD25+FOXP3+) are subsets of T cells which have an essential role in maintaining tolerance. OBJECTIVE: To evaluate peripheral Treg (CD4+; CD25+; FOXP3+) in children cohort with T1DM. METHODS: This study included 64 children diagnosed with T1DM and 35 age- and sex-matched healthy children as controls. All children were clinically evaluated and subjected to assessment of complete blood count (CBC), glycated hemoglobin, surface and cytoplasmic detection of Treg by flow cytometry. RESULTS: This study showed that the frequency of Treg (CD4+; CD25+; FOXP3+) was significantly lower in diabetic children than with normal controls (P<0.001). There was a significant (P <0.001) reduction in the Treg (CD4+; CD25+; FOXP3+) in T1DM children with uncontrolled (Hemoglobin A1c>7%) as compared to those with controlled (Hemoglobin A1c<7%) disease. CONCLUSION: Diminished Treg in T1DM proved that auto-reactivation of T-cell as a result of the breakdown of immune tolerance takes part in the elaboration of autoimmune disorders as T1DM. Treg may be used in immunotherapy, thus preventing T1DM development due to its pivotal role in immune tolerance.