FURIN, IFNL4, and TLR2 gene polymorphisms in relation to COVID-19 severity: a case-control study in Egyptian patients.

BACKGROUND AND AIM: A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis. METHODS: 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR. RESULTS: The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality. CONCLUSION: FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.

Interleukin 6 and interleukin 17A serum levels and gene- polymorphisms in the development of early allograft rejection in living donor liver transplant recipients.

The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.

Metabolic profiling during COVID-19 infection in humans: Identification of potential biomarkers for occurrence, severity and outcomes using machine learning.

BACKGROUND: After its emergence in China, the coronavirus SARS-CoV-2 has swept the world, leading to global health crises with millions of deaths. COVID-19 clinical manifestations differ in severity, ranging from mild symptoms to severe disease. Although perturbation of metabolism has been reported as a part of the host response to COVID-19 infection, scarce data exist that describe stage-specific changes in host metabolites during the infection and how this could stratify patients based on severity. METHODS: Given this knowledge gap, we performed targeted metabolomics profiling and then used machine learning models and biostatistics to characterize the alteration patterns of 50 metabolites and 17 blood parameters measured in a cohort of 295 human subjects. They were categorized into healthy controls, non-severe, severe and critical groups with their outcomes. Subject's demographic and clinical data were also used in the analyses to provide more robust predictive models. RESULTS: The non-severe and severe COVID-19 patients experienced the strongest changes in metabolite repertoire, whereas less intense changes occur during the critical phase. Panels of 15, 14, 2 and 2 key metabolites were identified as predictors for non-severe, severe, critical and dead patients, respectively. Specifically, arginine and malonyl methylmalonyl succinylcarnitine were significant biomarkers for the onset of COVID-19 infection and tauroursodeoxycholic acid were potential biomarkers for disease progression. Measuring blood parameters enhanced the predictive power of metabolic signatures during critical illness. CONCLUSIONS: Metabolomic signatures are distinctive for each stage of COVID-19 infection. This has great translation potential as it opens new therapeutic and diagnostic prospective based on key metabolites.

Should cancer treatment be continued during the COVID-19 pandemic? A single Egyptian institution experience.

The first confirmed case of coronavirus disease 2019 (COVID-19) in Egypt was reported on 14 February, 2020. Menoufia Clinical Oncology Centre is at the forefront of delivering care to patients with cancer during this public health crisis in Menoufia Governorate, Egypt. This article highlights the unique circumstances and challenges of cancer treatment during this global pandemic and the importance of organisational structure, preparation and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.