Clinical Performance of RT-PCR and Chest CT Scan for Covid-19 Diagnosis; A Systematic Review

Context: Due to their availability and rapid turnaround time, the supplemental role of chest computed tomography (CT) scan and real-time polymerase chain reaction (RT-PCR) is growing for early diagnosis of patients with COVID-19. However, due to the low efficiency of viral nucleic acid detection as well as low specificity of chest CT scan for detecting COVID-19 pneumonia, both methods show incomplete clinical performance for proper COVID-19 disease diagnosis. The purpose of this review was to compare the clinical performance of two methods and to evaluate the diagnostic values of chest CT scan and RT-PCR for suspected COVID-19 patients. Evidence acquisition: We systemically searched PubMed, Cochrane, from December 2019 to the end of April 2020. Clinical research papers in goal fields that reviewed COVID-19 patients, whom chest CT scan, and PCR testing were performed together were included. Results: In total, we found 536 studies; and finally168 studies were shortlisted. Following title and abstract screening, we reached 83 studies based on the inclusion and exclusion criteria. Conducted screen by the full text covered 28 studies, which led to data extraction. By the full-text assessment of 28 included studies, we found 4486 assessed patients. Totally, 3164 patients had positive chest CT scans, and 3014 patients had positive PCR results. The finding showed that recent studies on the diagnostic performance of RT-PCR and chest CT scan have commonly been reported from China. Conclusion: The results from this review indicate that the chest CT scan should be used for symptomatic and hospitalized patients. Moreover, chest CT scan should not be used as a primary screening tool for diagnosing COVID-19. Application of RT-PCR as the first line diagnosis is still recommended

Prevalence of blood-borne viruses among Iranian dentists: Results of a national survey

Objectives: Health care workers, including dentists, are at the front line for acquiring blood-borne virus infections. This study aimed to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency viruses among Iranian dentists. Material and Methods: The survey included 1628 dental health care workers who attended the 51st annual Congress of the Iranian Dental Association. Data on the risk of blood-borne virus transmission during health care and infection control practices were gathered from self-administered questionnaires. Sera were screened serologically by enzyme-linked immunosorbent assay (ELISA). The positive samples were examined by polymerase chain reaction (PRC) followed by direct sequencing. Results: Six (0.36) and 81 (5.0) were positive for hepatitis B surface antigen (HBsAg) and (anti-hepatitis B virus core antigen (anti-HBc), respectively. Only 1 (0.061) was positive for anti-hepatitis C virus (anti-HCV). No case was positive for anti-human immunodeficiency virus (anti-HIV). One case was diagnosed as being occult hepatitis B virus (HBV) infection. One thousand five hundred thirty-five (94.3) of participants had received at least 1 dose of HBV vaccine. One thousand three hundred fifty-nine (88.5) contained hepatitis B surface antibody (anti-HBs) > 10 IU/ml, of whom 55 (4.0) were anti-HBc positive, suggesting that they had been infected with HBV in the past. Anti-HBc positive cases had past histories of hepatitis, either their own or their spouses'. Individuals with inadequate anti-HBs levels (< 10 IU/ml) were significantly more prevalent among anti-HBc positive cases (p < 0.001). Conclusions: The prevalence of blood-borne viruses among dental HCWs found in this study was lower than past reports from Iranian dentists and general population. The implementation of HBV vaccination together with improvement in infection control procedures has reduced the potential for risk infection among Iranian dentists

Integrated analysis of gene expression profiles reveals deregulation of the immune response genes during different phases of chronic hepatitis B infection

© 2017, Kowsar Corp.Background: The natural history of chronic hepatitis B (CHB) infection is divided into different phases including immune tolerance (IT), immune clearance (or immune active [IA]), inactive carrier (IC), and reactivation. Despite utilizing high-throughput data, the distinct immunological mechanisms of these phases have been insufficiently investigated. Objectives: The aim of the present study was to determine candidate disease-associated genes and significantly altered biological processes for each phase of CHB infection. Methods: The gene expression profiles of 83 CHB patients (22 IT, 50 IA, and 11 IC phases) were obtained from gene expression omnibus (GEO dataset: GSE65359) and analyzed by bioinformatics tools. Several plugins of Cytoscape software were used to construct protein-protein interaction (PPI) networks and measure their topological properties. Subsequently, functional annotation and signaling pathway enrichment were carried out using the database for annotation, visualization and integrated discovery (DAVID) and Kyoto encyclopedia of genes and genomes (KEGG). Results: 449 and 452 deregulated genes were identified in IT-IA and IA-IC patients, respectively. Gene ontology and KEGG pathway analyses showed that several immune response-associated genes and signaling pathways (i.e. cytokine-cytokine receptor interaction, chemokine signaling pathway and T cell receptor signalling pathway) were upregulated in the IA phase, but downregulated in the IC phase. The LCK (encoding a tyrosine kinase) was determined as the most important hub gene of both constructed PPI networks. Furthermore, other immune response-associated genes such as CXCR3, VCAN, MYC, and STAT1 were found to be the important hub genes in clinical phases of CHB. Conclusions: The immune response-related pathways were found to be up and downregulated in the immune clearance phase and inactive carrier phase of CHB, respectively. The LCK hub gene might help the pathogenesis of different phases of CHB and serve as a therapeutic target for the treatment of hepatitis B virus

Regulatory network analysis of Epstein-Barr virus identifies functional modules and hub genes involved in infectious mononucleosis

© 2017, Springer-Verlag Wien.Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) – a hub gene with the highest centrality score – appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation

Evolution of hepatitis B virus surface gene and protein among Iranian chronic carriers from different provinces

Background and Objectives: Iranian chronic HBV carrier�s population has shown a unique pattern of genotype D distribution all around the country. The aim of this study was to explore more details of evolutionary history of carriers based on structural surface proteins from different provinces. Materials and Methods: Sera obtained from 360 isolates from 12 Different regions of country were used for amplification and sequencing of surface proteins. A detailed mutational analysis was undertaken. Results: The total ratio for Missense/Silent nucleotide substitutions was 0.96. Sistan and Kermanshah showed the lowest rate of evolution between provinces (P = 0.055). On the other hand, Khorasan Razavi and Khoozestan contained the highest ratio (P = 0.055). The rest of regions were laid between these two extremes. Azarbayjan and Guilan showed the highest proportion of immune epitope distribution (91.3 and 96, respectively). Conversely, Sistan and Tehran harbored the least percentage (66.6 and 68.8, respectively). Kermanshah province contained only 5.2, whereas Isfahan had 54.5 of B cell epitope distribution. In terms of T helper epitopes, all provinces showed a somehow homogeneity: 22.58 (Fars) to 46.6 (Khuzestan). On the other hand, distribution of substitutions within the CTL epitopes showed a wide range of variation between 6.6 (Khuzestan) and 63 (Kermanshah). Conclusion: Further to low selection pressure found in Iranian population, the variations between different regions designate random genetic drift within the surface proteins. These finding would have some applications in terms of specific antiviral regimen, design of more efficient vaccine and public health issues. © 2015, Tehran University of Medical Science. All rights reserved

A Comparative Analysis of Clinical Characteristics and Laboratory Findings of COVID-19 between Intensive Care Unit and Non-Intensive Care Unit Pediatric Patients: A Multicenter, Retrospective, Observational Study from Iranian Network for Research in Viral

Introduction: To date, little is known about the clinical features of pediatric COVID-19 patients admitted to intensive care units (ICUs).&nbsp;Objective: Herein, we aimed to describe the differences in demographic characteristics, laboratory findings, clinical presentations, and outcomes of Iranian pediatric COVID-19 patients admitted to ICU versus those in non-ICU settings.&nbsp;Methods: This multicenter investigation involved 15 general and pediatrics hospitals and included cases with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on positive real-time reverse transcription polymerase chain reaction (RT-PCR) admitted to these centers between March and May 2020, during the initial peak of the COVID-19 pandemic in Iran.&nbsp;Results: Overall, 166 patients were included, 61 (36.7%) of whom required ICU admission. The highest number of admitted cases to ICU were in the age group of 1–5 years old. Malignancy and heart diseases were the most frequent underlying conditions. Dyspnea was the major symptom for ICU-admitted patients. There were significant decreases in PH, HCO3 and base excess, as well as increases in creatinine, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and potassium levels between ICU-admitted and non-ICU patients. Acute respiratory distress syndrome (ARDS), shock, and acute cardiac injury were the most common features among ICU-admitted patients. The mortality rate in the ICU-admitted patients was substantially higher than non-ICU cases (45.9% vs. 1.9%, respectively; p&lt;0.001).&nbsp;Conclusions: Underlying diseases were the major risk factors for the increased ICU admissions and mortality rates in pediatric COVID-19 patients. There were few paraclinical parameters that could differentiate between pediatrics in terms of prognosis and serious outcomes of COVID-19. Healthcare providers should consider children as a high-risk group, especially those with underlying medical conditions

Hepatitis B virus genotype D is the only genotype circulating in Iranian chronic carriers, the unique pattern of genotypic homogeneity

Aim: To characterize the hepatitis B virus surface protein genotypes and sequence variations among HBsAg positive chronic Iranian patients from different ethnic groups. Method: The surface genes from 312 patients were amplified and directly sequenced. Results: All strains (100) belonged to genotype D and subtypes ayw2. The average nucleotide mutation frequency was 0.91 (dN/dS < 1.0), indicated negative selection. There was no significant correlation between HBV DNA and ALT levels and the occurrence of amino acid substitutions. However, in terms of HBeAg/Anti-HBe status, the association between both groups for silent nucleotide mutation was strong, indicating selection bias on missense mutations. A higher number of amino acid mutations was found in anti-HBe positive versus HBeAg positive patients.Conclusion: The uniqueness pattern of HBV genetics hemogeniety together with the low mutational frequency indicated that HBV has introduced to Iran recently and isolation of people in the absence of intermixing with other genotypes led to a homologous pattern. © 2014 ACT

Mutation hot spots in hepatitis B surface antigen in chronic carriers from Khoozestan Province, Southern of Iran

Mutations in the human hepatitis B virus (HBV) genome contribute to its escape from host immune surveillance and result in persistent infections. The aim of this study was to characterize the molecular variations of the surface gene and protein in chronically-infected patients from the southern part of Iran. The surface genes from 12 HBV chronic carriers were amplified, sequenced and subsequently aligned using international and national Iranian database. All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Of all 30 mutations occurred at 22 nucleotide positions, 18 (60%) were missense (amino acid altering) and 12 (40%) were silent (no amino acid changing). The mean mutation frequency (missense to silent nucleotide ratio), was 1.5, indicating application of a high positive selection pressure on the surface proteins. At the amino acid level, of 17 substitutions, 15 (88%) occurred in different immune epitopes within surface protein, of which 7 (46.6%) in B cell epitopes in 5 residues; 7 (46.6%) in T helper epitopes in 6 positions; 1 (7%) in inside CTL epitopes in 1 residue. We therefore conclude that the distribution of 93.2% of amino acid mutations inside B and T helper immune epitopes as well as the ratio between silent and missense nucleotide mutations showed a positive, focused immune selection pressure on the surface protein, which led to the evolution and emergence of escape mutants in these patients. Copyright© Autumn 2013, Iran J Allergy Asthma Immunol. All rights reserved.Peer Reviewe

Clinical Performance of RT-PCR and Chest CT Scan for Covid-19 Diagnosis; A Systematic Review

Context: Due to their availability and rapid turnaround time, the supplemental role of chest computed tomography (CT) scan and real-time polymerase chain reaction (RT-PCR) is growing for early diagnosis of patients with COVID-19. However, due to the low efficiency of viral nucleic acid detection as well as low specificity of chest CT scan for detecting COVID-19 pneumonia, both methods show incomplete clinical performance for proper COVID-19 disease diagnosis. The purpose of this review was to compare the clinical performance of two methods and to evaluate the diagnostic values of chest CT scan and RT-PCR for suspected COVID-19 patients.&nbsp;Evidence acquisition: We systemically searched PubMed, Cochrane, from December 2019 to the end of April 2020. Clinical research papers in goal fields that reviewed COVID-19 patients, whom chest CT scan, and PCR testing were performed together were included.&nbsp;Results: In total, we found 536 studies; and finally168 studies were shortlisted. Following title and abstract screening, we reached 83 studies based on the inclusion and exclusion criteria. Conducted screen by the full text covered 28 studies, which led to data extraction. By the full-text assessment of 28 included studies, we found 4486 assessed patients. Totally, 3164 patients had positive chest CT scans, and 3014 patients had positive PCR results. The finding showed that recent studies on the diagnostic performance of RT-PCR and chest CT scan have commonly been reported from China.&nbsp;Conclusion: The results from this review indicate that the chest CT scan should be used for symptomatic and hospitalized patients. Moreover, chest CT scan should not be used as a primary screening tool for diagnosing COVID-19. Application of RT-PCR as the first line diagnosis is still recommended