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.

Background: Toll-like receptor (TLR)-4 plays a vital role in recognizing viral particles, activating the innate immune system, and producing pro-inflammatory cytokines. Objectives: This cross-sectional study aimed to compare COVID-19 severity, progression, and fate according to TLR-4 (Asp299Gly) polymorphism in Egyptian patients. Methods: A total of 145 COVID-19 patients were included in this study. TLR-4 (Asp299Gly) genotyping was done using the PCR restriction fragment length polymorphism (PCR-RFLP) approach. Results: The most commonly encountered TLR-4 genotype in relation to the amino acid at position 299 was the wild-type AA (73.1%); meanwhile, the homozygous mutant GG genotype (8.3%) was the least encountered. At hospital admission, 85.8% of the AA group had free (with no ground glass opacities) chest computed tomography (CT) examination, and 16.0% SUMMARY were asymptomatic. On the other hand, of the AG and GG groups, 81.5% and 83.3%, respectively showed bilateral ground-glass opacities in chest CT, as well as 25.9% and 75.0%, respectively were dyspneic. Values of the total leucocytic count, C-reactive protein (CRP), ferritin, and D dimer increased in the AAAG>GG sequence. ICU admission (83.3%) and in-hospital death (33.3%) rates were significantly higher in the GG group. Conclusions: In COVID-19 patients, the TLR-4 mutant G allele may be associated with a more aggressive disease course and in-hospital death. New therapeutic alternatives could be aimed at this area.

Background:In coronavirus disease 2019 , finding sensitive biomarkers is critical for detecting severe cases early and intervening effectively. Aim of the work: To compare and evaluate the value of pretreatment c-reactive protein (CRP), interleukin-6 (IL-6), and their derived immune-inflammatory indices (CRP/albumin (CRP/alb), lymphocyte/CRP (L/CRP), and lymphocyte/IL-6 (L/IL-6)) in the prediction of COVID-19 severity and in-hospital mortality. Methods: This cross-sectional study included 85 confirmed COVID-19 patients, their complete blood count with differential, as well as albumin and IL-6 levels on the day of their hospital admission, were assessed and compared. We followed all patients till their inhospital death or discharge from the hospital. Results: On admission levels of CRP, IL-6, and CRP/alb were significantly higher (p=0.001) in severe patients and non-survivors, but L/CRP and L/IL-6 were significantly lower (p=0.001) compared to non-severe patients and nonsurvivors. CRP/alb and L/CRP at cut-offs of 1.65 and 260.86, respectively, were the best predictors for COVID-19 severity, while IL-6 and L/IL-6 at cut-offs of 120 pg/ml and 5.40, respectively, were the best predictors for COVID-19 in-hospital mortality. IL-6 was an independent risk factor associated with severe disease development (odds ratio (OR): 1.033; 95% confidence interval (CI): 1.002-1.066). Conclusions: Pretreatment levels of CRP, IL-6, and their derived indices should be included in the diagnostic work-up of COVID-19 to determine the severity and predict the outcome.

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.

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 (