COVID-19 susceptibility, severity, clinical outcome and Toll-like receptor (7) mRNA expression driven by TLR7 gene polymorphism (rs3853839) in middle-aged individuals without previous comorbidities.

Background: Toll-like receptors are implicated in the pathophysiology of the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory disease (MERS), according to several studies. The whole-genome sequencing of SARS-CoV-2 revealed that the TLR7 gene could be implicated in the virus's pathogenesis since the virus includes ssRNA patterns that could bind to TLR7. Aim: The purpose of this study was to look into the function of the TLR7 (rs3853839) C/G polymorphism and the expression of TLR7 mRNA transcript in the development, severity and progression of COVID-19. Subjects and methods: A case-control study included 285 participants who were divided into two groups: 150 middle-aged people with COVID 19 who had no previous co-morbidities and 135 healthy volunteers who served as controls. TaqMan test was used to genotype the TLR7 (rs3853839) C/G polymorphism, and real-time PCR was used to determine the relative expression of its mRNA transcript. The level of IL-6 in serum was determined using the ELISA method as an indicator of cytokine storm and COVID-19 severity. Results: The GG genotype was shown to be much more common in COVID-19 patients (38.7%) than controls (4.4%), with an OR of 19.86 (95% CI: 7.85; 50.22) and was linked to disease severity and poor clinical outcomes (hospitalization, respiratory failure, cardiac complications, ICU admission and mechanical ventilation).As a result, the G allele was considerably higher in cases (57.0%), while the C allele was significantly higher in controls (p = 0.001). The GG genotype was found to be substantially more common in patients who were severely/critically unwell. TLR7 mRNA expression levels were significantly higher in COVID-19 patients (2.44 ± 0.89) than in controls (1.06 ± 0.46) (p = 0.001). TLR7 mRNA levels were highest in COVID 19 patients with the GG genotype (rs3853839). Patients with the GG genotype had considerably lower WBC counts, but significantly higher serum ferritin, CRP, IL-6 and D dimer levels (P = 0.045, 0.001, 0.023, 0.033, 0.001, respectively). Conclusion: The GG form of the TLR7 SNP (rs3853839) could be a genetic risk factor for COVID-19 infection, severe illness and poor clinical outcome. TLR7 mRNA expression was also elevated in COVID-19 patients who were severely/critically unwell and had a bad outcome, suggesting that they could be used as COVID-19 prognostic biomarkers.

Potential impact of serpin peptidase inhibitor clade (A) member 4 SERPINA4 (rs2093266) and SERPINA5 (rs1955656) genetic variants on COVID-19 induced acute kidney injury.

Background: SARS-CoV-2 has a number of targets, including the kidneys. Acute Kidney Injury (AKI) might develop in up to a quarter of SARS-CoV-2 patients. In the clinical environment, AKI is linked to a high rate of death and leads to the progression of AKI to chronic renal disease. Aim: We aimed to investigate rs2093266 and rs1955656 polymorphisms in SERPINA4 and SERPINA5 genes, respectively, as risk factors for COVID-19 induced AKI. Subjects and methods: A case-control study included 227 participants who were divided into three groups: 81 healthy volunteers who served as controls, 76 COVID-19 patients without AKI and 70 COVID -19 patients with AKI. The TaqMan assay was used for genotyping the SERPINA4 (rs2093266) and SERPINA5 (rs1955656) polymorphisms by real-time PCR technique. Results: Lymphocytes and eGFR showed a significantly decreasing trend across the three studied groups, while CRP, d-Dimer, ferritin, creatinine, KIM-1and NGAL showed a significantly increasing trend across the three studied groups (P < 0.001). Rs2093266 (AG and AA) genotypes were significant risk factors among non-AKI and AKI groups in comparison to controls. Rs1955656 (AG and AA) were significant risk factors among the AKI group, while AA was the only significant risk factor among the non-AKI group. Recessive, dominant, co-dominant, and over-dominant models for genotype combinations were demonstrated. The GG v AA, GG + AG v AA, and GG v AG + AA models of the rs2093266 were all significant predictors of AKI, whilst only the GG v AA model of the rs1955656 SNP was a significant predictor. The logistic regression model was statistically significant, χ2 = 56.48, p < 0.001. AKI was associated with progressed age (OR = 0.95, 95% CI: 0.91-0.98, p = 0.006), suffering from chronic diseases (OR = 3.25, 95% CI: 1.31-8.01, p = 0.010), increased BMI (OR = 0.89, 95% CI: 0.81-0.98, p = 0.018), immunosuppressive (OR = 4.61, 95% CI: 1.24-17.16, p = 0.022) and rs2093266 (AG + AA) (OR = 3.0, 95% CI: 1.11-8.10, p = 0.030). Conclusion: Single nucleotide polymorphisms (rs2093266) at SERPINA4 gene and (rs1955656) at SERPINA5 gene were strongly linked to the development of AKI in COVID-19 patients.