Background:The clinical spectrum of COVID-19 is extremely variable. Thus, it is likely that the heterogeneity in the genetic make-up of the host may contribute to disease severity. Toll-like receptor (TLR)-4 plays a vital role in the innate immune response to SARS-CoV-2 infection. The susceptibility of humans to severe COVID-19 concerning TLR-4 single nucleotide polymorphisms (SNPs) has not been well examined. Objective: The goal of this research was to investigate the association between TLR-4 (Asp299Gly and Thr399Ile) SNPs and COVID-19 severity and progression as well as the cytokine storm in Egyptian patients. Methods: We genotyped 300 adult COVID-19 Egyptian patients for TLR-4 (Asp299Gly and Thr399Ile) SNPs using PCR-restriction fragment length polymorphism (PCR-RFLP). We also measured interleukin (IL)-6 levels by enzyme-linked immunosorbent assay (ELISA) as an indicator of the cytokine storm. Results: The minor 299Gly (G) and 399Ile (T) alleles were associated with a significant (P < 0.001) positive risk of severe COVID-19 (OR = 3.14; 95% CI = 2.02-4.88 and OR = 2.75; 95% CI = 1.66-4.57), their frequency in the severe group were 71.8% (84/150) and 70.7% (58/150), respectively. We detected significant differences between TLR-4 (Asp299Gly, Thr399Ile) genotypes with regard to serum levels of IL-6. Levels of IL-6 increased significantly with the presence of the mutant 299Gly (G) and 399Ile (T) alleles to reach the highest levels in the Gly299Gly (GG) and the Ile399Ile (TT) genotypes (170 pg/mL (145-208.25) and 112 pg/mL (24-284.75), respectively). Conclusion:The TLR-4 (Asp299Gly and Thr399Ile) minor alleles 299Gly (G) and 399Ile (T) are associated with COVID-19 severity, mortality, and the cytokine storm.

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Objectives: Dysregulation of the immune response appears to play a significant role in recurrent aphthous stomatitis (RAS) development. The main objective of this case–control study is to investigate the blood levels of mannose-binding lectin (MBL) and the frequency of the MBL2 gene (gly54asp) polymorphism in RAS patients, including 40 RAS patients and 40 healthy controls. Methods: Serum MBL levels were determined by ELISA, while the PCR-restriction fragment length polymorphism was used in MBL2 genotyping. Results: The median serum MBL level was significantly lower in the RAS group than in the control group (975 ng/mL (545–1320) vs. 1760 ng/mL (1254–2134); p≤ 0.001). The MBL levels were significantly lower in the BB genotype, whereas they were significantly higher in the wild type AA with a median of 525 and 1340 ng/mL, respectively ( p =0.005). The B allele was expressed in significantly higher percentages of RAS patients than in controls. There was no significant association between MBL serum levels ( p=0.685) or MBL2 codon 54 genotypes ( p=0.382) with the type of ulcers. Conclusion: There was an association between low MBL serum levels and the variant allele B of the MBL2 (gly54asp) gene, and the susceptibility to RAS. As a result, potential novel therapeutic options for RAS patients with MBL deficiency should be investigated.

Background: Increased intestinal permeability, either due to the exposure to antigens in asthmatic patients or due to a barrier defect, play a critical role in susceptibility to environmental allergens. House dust mites allergy occurs more commonly than any other allergens among Egyptian asthmatic patients.Aim:To assess the relation between serum zonulin level as a marker of increased intestinal permeability and the severity of house dust mites allergic asthma.Methods:A case control study which included 48 house dust mites allergic asthma and 48 healthy control subjects attending the allergy and immunology unit, microbiology and immunology department, Faculty of medicine, Zagazig University. Results:On comparing the 2 studied groups, there was a statistically significant difference between the 2 groups concerning serum IgE and serum zonulin levels ( p=0.000, 0.000 respectively)The mean serum zonulin was equal to 258.3±153.01 ng/ml in the asthmatic group and 80±13 ng/ml in the control group. Serum zonulin level significantly increased with the increase of asthma severity (p˂0.001). The cut off value of serum zonulin was ≥ 198 ng/ml, and the area under the curve was 0.76. It displayed sensitivity equal to 80% and specificity equal to 71.4%. Its negative predictive value was equal to 83.3%. Conclusion: Intestinal barrier dysfunction contributes in the pathogenesis of allergic asthma. Serum zonulin level reflects an increase in intestinal permeability and acts as prognostic factor of severity in Asthma. Correction of the gut barrier defect may be an additional novel approach for Asthma.

Background Increased intestinal permeability, either due to the exposure to antigens in asthmatic patients or due to a barrier defect, plays a critical role in susceptibility to environmental allergens. House dust mite allergy occurs more commonly than any other type of allergy among Egyptian asthmatic patients. Aim To assess the relation between serum zonulin level as a marker of increased intestinal permeability and the severity of house dust mite allergic asthma. Methods A case–control study which included 48 patients with house dust mite allergic asthma and 48 healthy control subjects attending the Allergy and Immunology Unit, Microbiology and Immunology Department, Faculty of Medicine, Zagazig University. Results A statistically significant difference was detected between the two studied groups with respect to serum IgE and serum zonulin levels (p ˂ 0.001 and ˂ 0.001, respectively). The mean serum zonulin was equal to 258.3 ± 153.01 ng/ml in the asthmatic group and 80 ± 13 ng/ml in the control group. Serum zonulin level significantly increased with the increase of asthma severity (p ˂ 0.001). The cut off value of serum zonulin was ≥ 198 ng/ml, and the area under the curve was 0.76. It displayed sensitivity equal to 80% and specificity equal to 71.4%. Its negative predictive value was equal to 83.3%. Conclusion Intestinal barrier dysfunction contributes to the pathogenesis of allergic asthma. Serum zonulin level reflects an increase in intestinal permeability. Zonulin acts as prognostic factor of severity in asthma. Correction of the gut barrier defect may have a potential positive prognostic effect in asthma.

Background: Early detection of COVID-19 patients with potentially severe disease is crucial for predicting the disease's course and prioritizing medical resources, lowering overall disease mortality. Objectives: To explore the role of baseline hemogram-derived ratios and systemic-immune inflammation index (SII), in addition to C-reactive protein (CRP), in predicting COVID-19 severity and prognosis. Methods: In this retrospective study, data were collected from the medical records of 425 COVID-19 patients. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and SII, together with the CRP, were investigated and compared. Results: NLR, PLR, SII, and CRP increased significantly in severe cases and with ICU admission (p ≤ 0.001). But, in nonsurvivors, only NLR and CRP were significantly elevated (p<0.05). By interpreting area under the receiver operating characteristic curve (ROC-AUC), CRP and NLR were better predictors of disease severity (AUC: 0.7 for both), the need for ICU admission (AUC: 0.763 and 0.727, respectively), and in-hospital mortality (AUC: 0.812 and 0.75, respectively). SII was significantly associated with the risk of severe disease development (odds ratio (OR): 3.143; 95% confidence interval (

Background: Early detection of COVID-19 patients with potentially severe disease is crucial for predicting the disease's course and prioritizing medical resources, lowering overall disease mortality. Objectives: To explore the role of hemogram-derived ratios and systemic-immune inflammation index (SII), in addition to C-reactive protein (CRP), in predicting COVID-19 severity and prognosis. Methods: In this retrospective study, data were collected from the medical records of 425 COVID-19 patients. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and SII, together with the CRP, were investigated and compared. Results: NLR, PLR, SII, and CRP increased significantly in severe cases and with ICU admission (p ≤ 0.001). But, in non-survivors only NLR and CRP were significantly elevated (p < 0.05). By interpreting area under the receiver operating characteristic curve (ROC-AUC), CRP and NLR were better predictors of disease severity (AUC: 0.7 for both), the need for ICU admission (AUC: 0.763 and 0.727, respectively) and in-hospital mortality (AUC: 0.812 and 0.75, respectively). SII was significantly associated with the risk of severe disease development (odds ratio (OR): 3.143; 95% confidence interval (CI): 1.101-8.976); CRP (OR: 2.902; CI95%: 1.342-6.273) and NLR (OR: 2.662; CI95%, 1.072-6.611) were significantly associated with ICU admission risk; and only CRP was significantly associated with in-hospital mortality risk (OR: 3.988; CI95%: 1.460-10.892). Conclusions: Values of CRP, SII, and NLR at the time of hospital admission could be independent prognostic biomarkers to predict COVID-19 progression. The integration of CRP, SII, and NLR into prognostic nomograms may lead to improved prediction.

Introduction: Irritable bowel syndrome (IBS) is a gastrointestinal disorder due to enteric nervous system impairment that produces different patterns of digestion. IBS is a common finding in diabetic patients. The functions of lncRNAs in IBS are still not clear and need to be further investigated. The aim of this study was to assess the diagnostic roles of lncRNA H19 and TUG1 for IBS associated with diabetes and to evaluate their association with clinical and laboratory findings. Subjects and Methods: Samples from 42 diabetic patients, 42 diabetic patients with IBS, and 42 healthy controls were obtained. The LncRNA H19 and TUG1 expressions were measured by quantitative real-time PCR. Results: The patients with IBS had significantly lower levels of lncRNA H19 and TUG1 expression than the healthy controls and diabetic-only patients (p < 0.001). LncRNA H19 and TUG1 can discriminate between diabetic-only patients and those with IBS (areas under the ROC curves of 0.95 and 0.722, respectively). The TUG1 expression levels were significantly different among types of IBS (IBS-D lower than IBS-M and IBS-C lower than IBS-M; p = 0.0165 and p = 0.043, respectively). H19 and TUG1 were downregulated in patients with poor glycemic control. lncRNA H19 and TUG1 expression in diabetic patients with IBS significantly negatively correlated with the IBS severity scoring system. Both lncRNAs’ expression significantly predicted the disease severity. LncRNA H19 expression can be an independent predictor for disease severity (adjusted odds ratio = 0.00001, 95% CI = 0–0.5, p = 0.045). Conclusions: Diabetic patients with IBS had significantly lower levels of lncRNA H19 and TUG1 expression than healthy controls and diabetic-only patients. LncRNA H19 had better diagnostic performance criteria for IBS. LncRNA H19 expression can be an independent predictor for IBS severity.