Association of Interleukin-6 (rs1800795) and Interleukin-10 (rs1800896) Genetic Polymorphisms with the Outcome of COVID-19 Infection: A Single Center Study.

The corona virus disease-2019 (COVID-19) pandemic has affected most of the world with varying degrees of morbidity and mortality. The presence of genetic polymorphisms may be associated with the severity and outcome of COVID-19 infection. This work aimed to evaluate the genetic polymorphisms of interleukin (IL-6) and IL-10 genes with the outcome of COVID-19 infection. This cross-sectional study was conducted on 354 patients who were classified into moderate and severe cases (including alive and deceased cases). All individuals were genotyped for one SNP for IL-6 (rs1800795) and one SNP for IL10 (rs1800896) using allelic discrimination real-time PCR technique. In this study, 198 cases were moderate, and 156 cases were severe. The risk of allele carriage of the minor allele of IL-6 rs1800795 (C) was significantly higher among the severe group when compared with that of the moderate group (p < 0.0001), while there was a mild significant difference of same allele carriage among alive cases when compared to that of deceased one (p < 0.04). Furthermore, the risk of the C allele of IL-10 rs1800896 was significantly increased in severe cases when compared with the moderate group (p < 0.0001), while there was no significant difference of the risk of the C allele in deceased cases when compared with that of alive ones (p > 0.05). In conclusion, the C allele (rs1800795) of IL-6 and the C allele (rs1800896) of IL-10 were highly significant in severe cases than in moderate cases. The C allele carriage of IL-6 showed only a significant difference between alive and deceased patients and not with the C allele of IL-10.

Characterization of a breakthrough vaccine escape strain associated with overt hepatitis B virus infection.

Hepatitis B virus (HBV) vaccine is composed of the purified hepatitis B surface antigen (HBsAg) that is produced by recombinant DNA technology. The neutralizing antibodies induced by vaccination target mainly the "a" determinant, aa124-147, of the outer viral envelope (HBsAg). In the present work, we demonstrate a case study for vaccinated patient that is infected with a vaccine escape HBV strain (Eg200). Characterization of the isolate Eg200 showed that it belongs to the genotype D and an uncommon sub-genotype in Egypt; D9. The DNA sequence encoding HBsAg was sequenced. Mutational analysis of the HBsAg showed a double mutation in the "a" determinant of this HBV isolate; T125M and P127T. However, such substitutions were found to be conserved to the detected serotype, ayw3, of Eg200 isolate. This case report indicates that continuous characterization of breakthrough vaccine escape strains of HBV is essential to develop the immunization strategies against HBV infection.

Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients.

Background Parasites are well-known immune-modulators. They inhibit some aspects of the immune system to ensure persistence inside the host for a long time; meanwhile, they stimulate other immune aspects to assure the survival of the host. Wide variations in the severity of coronavirus disease 2019 (COVID-19) among developed and developing countries were reported during the COVID-19 pandemic. Parasitic infections, including Toxoplasma gondii (T. gondii), were claimed to contribute to such variations. Methods To explore a possible relationship between latent toxoplasmosis and COVID-19 severity, our study included 44 blood samples from moderate/severe COVID-19 patients, who were admitted to Mansoura University Hospitals, Egypt, during the pandemic. Patients' sera were screened for Toxoplasma IgG antibodies using ELISA (Roche Diagnostics, Indianapolis, USA), and the gene expression of important immune markers (iNOS, arginase-1, IFN-γ, TNF-α, IL-6, IL-10, and TGF-ß) was checked using real-time quantitative PCR. Clinical and laboratory data were obtained from the patients' medical records. Results Toxoplasma IgG antibodies were detected in 33 (75%) of patients. None of the studied clinical or laboratory parameters showed any significant changes in relation to toxoplasmosis seroprevalence. Further classification of the patients according to COVID-19 severity and Toxoplasma seroprevalence did not reveal any changes related to toxoplasmosis as well. Conclusion Our study indicates that latent toxoplasmosis has no effect on the severity of COVID-19.

Efficacy of combined Sofosbuvir and Daclatasvir in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study.

BACKGROUND: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. We aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia. RESEARCH DESIGN AND METHODS: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory, and radiological data were collected at baseline, after 7, 14, and 28 days of therapy. Primary endpoint was rate of clinical/virological cure. RESULTS: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After 1 month of therapy, no differences were found in rates of ICU admission, oxygen therapy, or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P < 0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P < 0.01) were noticed in group (A). CONCLUSION: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.

Natural variability in surface antigen and reverse transcriptase domain of hepatitis B virus in treatment-naïve chronic HBV-infected Egyptian patients.

Hepatitis B virus (HBV) infection is a serious health problem not only in Egypt, but also worldwide. We collected 57 serum samples from treatment-naïve chronic HBV-infected Egyptians. The DNA segment encoding HBV surface antigen (HBsAg) and reverse transcriptase (RT) domain was partially sequenced. Our data revealed that all viral isolates belonged to genotype D with ayw2 as the predominant serotype (89 %). Regarding HBsAg, 45 substitutions were detected in the collected isolates. Eleven substitutions were found in the major hydrophilic region, including two novel ones (M103T and G130E) that were not correlated before with genotype D. Additionally, 11 occult samples (19 %) were detected, in which the predominant mutations of HBsAg were S143L (7 samples) followed by D144A and T125M (4 samples each). Concerning the RT domain, 26 isolates (45 %) harbored 19 natural mutations that were reported to be associated with antiviral resistance. Eleven different mutations were not correlated previously with genotype D. The most predominant mutation was Y124H (47 samples, 82 %). Interestingly, such mutation was detected in 91 % of the previous reported sequences of HBV isolates collected in Egypt (157 sequences). Furthermore, our study illustrated the presence of viral quasispecies in the HBsAg (10 samples, 17.5 %) and RT domain (9 samples, 15.7 %). In conclusion, we elucidated the presence of natural substitutions in HBsAg and RT domain of HBV isolates obtained from treatment-naïve chronic HBV-infected Egyptian patients. Additionally, we detected viral quasispecies and revealed Y124H as a characteristic substitution in the RT domain for HBV isolates in Egypt. Moreover, novel substitutions in HBsAg and RT domain were reported with genotype D.

Cognitive impairment and neuropsychiatric manifestations of neurobrucellosis.

AIM: This study aimed to reveal insight into the unclear areas of the diagnosis in neurobrucellosis and to decide the neuropsychiatric manifestations and cognitive impairment among patients with brucellosis. METHODS: 82 patients with serologically confirmed brucellosis were included and divided into two groups according to the neuropsychiatric manifestations, the first group included 18 patients with neurobrucellosis and the second group included 64 patients with non-neurobrucellosis. Both groups were compared regarding the general symptoms and neurological symptoms and signs. Cognitive impairment in both groups was assessed by Montreal-Cognitive Assessment (MoCA), Wechsler Memory Scale-Revised (WMS-R), and forward and backward digital test. Also, depression and anxiety were assessed by Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: 18 (21.9%) patients were diagnosed as neurobrucellosis and 64 (78.1%) patients were diagnosed as non-neurobrucellosis. The mean age of the total patients was 34.91 ± 14.74, consisted of 45 males and 37. Most of the patients were living in rural areas 60 patients (74.4%). The most significantly higher neurological symptoms in neurobrucellosis patients were confusion and headache (P = 0.008 and P = 0.01, respectively). While the most significant higher neurological signs were loss of orientation (P = 0.009), muscle weakness (P = 0.04), neck rigidity (P < 0.05), pyramidal signs, and lost deep reflexes (P < 0.05). The neurobrucellosis patients had significantly impaired cognition in comparison with nonneurobrucellosis patients and more psychiatric signs like behavioral changes, anxiety, and depression (P < 0.001, P < 0.001, and P = 0.01, respectively). CONCLUSIONS: Patients with neuropsychiatric manifestations and cognitive impairment should be considered for neurobrucellosis and should receive proper therapy.

Alterations of the Treatment-Naive Gut Microbiome in Newly Diagnosed Hepatitis C Virus Infection.

Gut microbiota dysbiosis has been linked to many heath disorders including hepatitis C virus (HCV) infection. However, profiles of the gut microbiota alterations in HCV are inconsistent in the literature and are affected by the treatment regimens. Using samples collected prior to treatment from newly diagnosed patients, we characterized the gut microbiota structure in HCV patients as compared to healthy controls. Treatment-naive HCV microbiota showed increased diversity, an increased abundance of Prevotella, Succinivibrio, Catenibacterium, Megasphaera, and Ruminococcaceae, and a lower abundance of Bacteroides, Dialister, Bilophila, Streptococcus, parabacteroides, Enterobacteriaceae, Erysipelotrichaceae, Rikenellaceae, and Alistipes. Predicted community metagenomic functions showed a depletion of carbohydrate and lipid metabolism in HCV microbiota along with perturbations of amino acid metabolism. Receiver-operating characteristic analysis identified five disease-specific operational taxonomic units (OTUs) as potential biomarkers of HCV infections. Collectively, our findings reveal the alteration of gut microbiota in treatment naive HCV patients and suggest that gut microbiota may hold diagnostic promise in HCV infection.

Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Can Triggering Receptors Expressed on Myeloid Cells be used for Diagnosis of Salmonella Typhi Infection?

BACKGROUND: There is a need for rapid and accurate diagnostic biomarker for diagnosis of Salmonella fever. AIMS: The aim of the present study was to assess the importance of procalcitonin (PCT), Soluble Triggering Receptors expressed on Myeloid Cells 1 (sTREM1) and C- reactive protein (CRP) in the diagnosis of enteric fever with positive blood culture for S.typhi. METHODS: Blood samples were withdrawn from 200 patients with suspected enteric fever and subjected for the determination of CRP, PCT and sTREM-1. RESULTS: The sensitivity and specificity for PCT cut off were 97.7% & 82.5%, for CRP the sensitivity and specificity were 95.3% and 77% and for s-TREM-1 the sensitivity and specificity were 95.3% & 77%. CONCLUSION: S-TREM-1 may be considered as a novel biomarker for the diagnosis of enteric fever with good sensitivity and specificity.

Impact of Toll-like Receptors 2(TLR2) and TLR 4 Gene Variations on HCV Susceptibility, Response to Treatment and Development of Hepatocellular Carcinoma in Cirrhotic HCV Patients.

Background and Aims: Genetic polymorphisms of Toll-like receptors (TLRs) have been proposed to affect susceptibility to HCV infection and progression to end-stage liver disease. This study was conducted to clarify the association of SNPS of TLR2 and TLR4 with clinical outcome of hepatitis C, response to treatment and development of HCC.Methods: The current study examined 3295 individuals from 725 families that were categorized into groups comprising chronic HCV (CH), spontaneous viral clearance (SC) and control subjects. Treated patients were classified into responders (RT) and non-responders (NRT). In addition, patients with liver cirrhotic (LC), and hepatocellular carcinoma (HCC) were also included. All subjects were genotyped for five single nucleotide polymorphisms (SNPs) of TLR2 and four SNPs of TLR4 and their haplotypes using allelic discrimination real-time PCR.Results: Results demonstrated strong association with allele A of rs13105517 of TLR2 and allele C of rs10116253 of TLR4 with CH in comparison to SC group. However, The peak of risk of HCC was observed with allele C of rs3804099 of TLR2 and C allele of rs10116253 TLR4 (p < 0.001).A strong association was found with allele T of rs1816702 of TLR2 and allele A of rs5030728 of TLR4 in non responder group in comparison to responders (p < 0.001). Haplotypes CAGT of TLR4 and ATAC of TLR2 showed significant association with CH and HCC groups in comparison to other groups.Conclusions: This study shows an association of minor alleles of TLR2 and TLR4 with outcome of HCV infection, response to therapy and development of HCC in cirrhotic patients.

Molecular analysis of Hepatitis B virus sub-genotypes and incidence of preS1/preS2 region mutations in HBV-infected Egyptian patients from Mansoura.

Hepatitis B virus (HBV) is one of the major causes of viral hepatitis worldwide. Despite the prevalence of HBV infection in Egypt, few studies have focused on sub-genotyping of the virus. Moreover, no studies are available regarding the mutational analysis of the preS1/preS2 region of the viral genome, or its impact on hepatocellular carcinoma (HCC) development in Egypt. In this study, we have analyzed the sub-genotypes and incidence of mutations in the preS1/preS2 region of HBV present in HBV-infected patients, from Mansoura city (located in the center of Nile Delta region of Egypt), via partial sequencing of this specific region. Moreover, we have investigated the impact of these mutations on HCC development by measuring serum alpha fetoprotein (AFP) level and abdominal ultrasound examination of the HBV-infected patients. According to our results, all samples were genotype D in which sub-genotype D1 was predominant. In addition, the results revealed mutations in the preS1/preS2 region, which could result in either immature preS1 protein or completely inhibit the translation of the preS2 protein. However, there was no incidence of HCC development in patients infected with mutated HBV in the preS1/preS2 region. In summary, for the first time our work has proved the predominance of sub-genotype D1 among HBV-infected Egyptian patients in Mansoura city, Nile Delta region, Egypt, and incidence of mutations in the preS1/preS2 region of HBV genome. This current study opens up research opportunities to discuss the impact of HBV mutations on the development of HCC in Egypt.

New Cutoff Point for Platelet Count/Spleen Diameter Ratio to Predict Esophageal Varices in Patients with Hepatitis C Virus-related Hepatic Cirrhosis.

The esophagogastroduodenoscopy (EGD) with all its hazards remains the gold standard screening tool for esophageal varices. Noninvasive tools have been proposed and studied to replace the EGD. Platelet count (PC)/spleen diameter (SD) ratio as a noninvasive tool for predicting the presence of esophageal varices was proposed and studied in many previous studies. HOW TO CITE THIS ARTICLE: El-Sherbiny W, Elegezy M, Shaltout SW. New Cutoff Point for Platelet Count/ Spleen Diameter Ratio to Predict Esophageal Varices in Patients with Hepatitis C Virus-related Hepatic Cirrhosis. Euroasian J Hepato-Gastroenterol 2015;5(2):136-137.