The pandemic coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID‐19 are underway. Respiratory viral infections, such as influenza, predispose patients to co‐infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co‐infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS‐CoV‐2). Although antibiotics do not directly affect SARS‐CoV‐2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co‐infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co‐infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID‐19. Also, the antibiotic‐resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co‐infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID‐19.

The diagnosis of cryptogenic liver disease is made when after extensive evaluations, recognizable etiologies of chronic liver disease are excluded. In this study, the presence of hepatitis C virus (HCV) RNA was tested in peripheral blood mononuclear cells (PBMCs) taken from Iranian patients who although were found negative for plasma HCV RNA and anti-HCV antibodies, suffered from chronic liver disease of unknown etiology. From September 2007 to March 2010, 69 patients from Tehran with chronic liver disease of unknown etiology who were referred to our center were enrolled in the present study. PBMCs were isolated from 10 mL peripheral blood specimens. HCV-RNA status was tested in plasma and PBMCs samples by reverse-transcription polymerase chain reaction (RT-PCR). HCV-RNA was detected in HCV-positive PBMCs specimens by RT-PCR method. HCV genotypes were subsequently analyzed in HCV-positive samples using restriction fragment length polymorphism (RFLP) assay; then HCV genotypes were confirmed by sequencing of 5' non-coding fragments after cloning PCR products into pJET1.2/blunt cloning vector. HCV-RNA was detected in PBMCs specimens belonging to 7 (10%) out of 69 patients. Genotyping of the HCV-RNA isolated from PBMCs showed that 3 (43%) patients with occult HCV infection had genotype 1b, 2 (29%) had genotype 1a, and another 2 (29%) had genotype 3a. The results of this study suggest that patients with chronic liver disease of unknown etiology may have occult HCV infection in the absence of anti-HCV antibodies and plasma HCV-RNA. It has been suggested that in the absence of liver biopsy specimens, analysis of PBMC sample for HCV-RNA would be informative.

BackgroundHepatitis C virus (HCV) has different genotypes throughout the world. Since the determination of which antiviral treatment to be applied is related to HCV genotypes, identification of an individual’s HCV genotypes prior to antiviral therapy is critical.ObjectivesThe purpose of this study was to investigate the distribution of HCV genotypes in a large population of Iranian HCV infected patients.Patients and MethodsEleven thousand, five hundred and sixty one patients with chronic HCV infection which referred to hospitals related to the Tehran University of Medical Sciences and Tehran Hepatitis Center-Clinical Department of Baqiyatallah Research Center for Gastroeneterology and Liver Disease from March 2003 to December 2011 were enrolled. Following extraction of viral RNA of the serum, HCV-RNA was detected using reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and then HCV genotypes analyzed by restriction fragment length polymorphism (RFLP) assay.ResultsThe mean age of patients was 37.6 ± 14.2 years (range: 1-87). The highest frequency was noted for subtype 1a (44.9%) followed by subtype 3a (39.6%), and 1b (11.3%). Mixed HCV genotypes were also found in 2.5% of the total cases. Subtype 1a was the most frequent genotype in patients over 40 years of age (46.1% versus 42.4%) and subtype 3a was the most frequent in patients under 40 years old (41.5% versus 38.9%).ConclusionsThis study suggested that the dominant HCV subtype among Iranian patients was 1a followed by subtype 3a.

BackgroundA strong association between obesity and non-alcoholic fatty liver disease (NAFLD) has been reported.ObjectivesThis study was conducted to evaluate if new obesity indices, including a body shape index (ABSI) and body roundness index (BRI), have stronger associations with NAFLD than waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR).MethodsIn this cross-sectional study, we utilized the data of 4,872 participants aged 18 - 74 years from a cohort study conducted among 6,143 subjects in northern Iran. Logistic regression analysis was performed on NAFLD as the outcome and obesity measures (based on Z-score values) as potential predictors. Receiver operating characteristic (ROC) analyses were conducted, in which NAFLD was considered as a reference variable and obesity measures as classification variables. The discriminatory ability of the obesity measures was reported based on area-under-the-curves, and the related cut-off points of BRI and WHtR were determined using the Youden index (YI).ResultsBased on our results, BRI (OR = 5.484 for men and OR = 3.482 for women) and WHtR (OR = 5.309 for men and OR = 3.854 for women) showed a higher association with NAFLD than ABSI (OR = 1.363 for men and OR = 1.003 for women) and WHR (OR = 3.123 for men and OR = 1.628 for women). The optimal cut-off points for BRI were 4.00 (sensitivity = 82.7%, specificity = 70.8%) for men and 5.00 (sensitivity = 83.3%, specificity = 71.7%) for women. The optimal cut-off points for WHtR were 0.533 (sensitivity = 82.7%, specificity = 70.8%) for men and 0.580 (sensitivity = 83.3%, specificity = 71.7%) for women.ConclusionsWhile BRI and WHtR have equally strong associations with NAFLD, ABSI and WHR have weaker associations with NAFLD than BRI and WHtR.

Persistent anemia is a known consequence of Parvovirus B19 (B19) infection following renal transplantation. However, to date, no description of B19-related hemophagocytic lymphohistiocytosis (HLH) exists in renal transplant recipients. We report a 24-year-old male kidney recipient, who presented with fever, severe anemia and allograft dysfunction two years following transplantation. Hyperferritinemia, hypertriglyceridemia, elevated serum lactate dehydrogenase, pancytopenia and fragmented red blood cells on the peripheral blood were also noted. Bone marrow examination revealed giant pronormoblasts and frequent histiocytes with intracellular hematopoietic elements, consistent with HLH. Renal allograft biopsy revealed closure of the lumen of glomerular capillaries and thickening of the capillary walls compatible with thrombotic microangiopathy. The presence of anti-B19 IgM antibody and viral DNA in the patient's serum (detected by real-time PCR) confirmed an acute B19 infection. Following high-dose intravenous immunoglobulin therapy, the anemia gradually resolved and renal function improved. As far as we know, this is the first report of B19-associated HLH and thrombotic microangiopathy in a renal transplant recipient.

Virus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T cell epitope repertoire and mechanisms of CD8 T cell failure in HDV infection have been poorly characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impacts of viral mutations on immune escape. In this study, we predicted peptide epitopes binding the most frequent human leukocyte antigen (HLA) types and assessed their HLA binding capacities. These epitopes were characterized in HDV-infected patients by intracellular gamma interferon (IFN-γ) staining. Sequence analysis of large hepatitis delta antigen (L-HDAg) and HLA typing were performed in 104 patients. The impacts of substitutions within epitopes on the CD8 T cell response were evaluated experimentally and by studies. We identified two HLA-B*27-restricted CD8 T cell epitopes within L-HDAg. These novel epitopes are located in a relatively conserved region of L-HDAg. However, we detected molecular footprints within the epitopes in HLA-B*27-positive patients with chronic HDV infections. The variant peptides were not cross-recognized in HLA-B*27-positive patients with resolved HDV infections, indicating that the substitutions represent viral escape mutations. Molecular modeling of HLA-B*27 complexes with the L-HDAg epitope and its potential viral escape mutations indicated that the structural and electrostatic properties of the bound peptides differ considerably at the T cell receptor interface, which provides a possible molecular explanation for the escape mechanism. This viral escape from the HLA-B*27-restricted CD8 T cell response correlates with a chronic outcome of hepatitis D infection. T cell failure resulting from immune escape may contribute to the high chronicity rate in HDV infection. Hepatitis delta virus (HDV) causes severe chronic hepatitis, which affects 20 million people worldwide. Only a small number of patients are able to clear the virus, possibly mediated by a virus-specific T cell response. Here, we performed a systematic screen to define CD8 epitopes and investigated the role of CD8 T cells in the outcome of hepatitis delta and how they fail to eliminate HDV. Overall the number of epitopes identified was very low compared to other hepatotropic viruses. We identified, two HLA-B*27-restricted epitopes in patients with resolved infections. In HLA-B*27-positive patients with chronic HDV infections, however, we detected escape mutations within these identified epitopes that could lead to viral evasion of immune responses. These findings support evidence showing that HLA-B*27 is important for virus-specific CD8 T cell responses, similar to other viral infections. These results have implications for the clinical prognosis of HDV infection and for vaccine development.

This study indicates that the dominant HCV genotype among patients living in Tehran was 1a.

Infection with the adenovirus type 2 ts1 mutant at the nonpermissive temperature resulted in the production of noninfectious virions. This has been ascribed to the P137L mutation in the virus-encoded cysteine protease which causes a defect in protease activity. Here we have examined the ts1 defect in detail as a means of learning more about the viral protease. The ts1 protease accumulated in the nucleus normally and was found associated with incomplete particles as was the case with wt. This enzyme was active in both wt and ts1 incomplete particles produced at 39 degrees (ts1-39 TCs), provided they were dissociated with 4 M urea. While the wt protease was packaged into complete particles, the ts1-39 particles were totally devoid of protease. This defect was nearly completely corrected by addition of the 11-residue activating peptide PVIc (GVQSLKRRRCF) to the medium late in infection. Rescue of ts1 occurred via restoration of enzyme activity and packaging of the ts1 enzyme into complete virions. Recombinant ts1 enzyme was not temperature sensitive. The P137L mutation responsible for the ts1 defect appeared therefore to be an in vivo phenotype involving apparently linked events of protease packaging and activation mediated by the PVI protein.