The impact understanding of exosome therapy in COVID-19 and preparations for the future approaches in dealing with infectious diseases and inflammation.

Cytokine storms, which result from an abrupt, acute surge in the circulating levels of different pro-inflammatory cytokines, are one of the complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess the effect of exosomes on the release of pro-inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19) and compare it with a control group. The cytokines evaluated in this study were TNF-α, IL-6, IL-17, and IFN-γ. The study compared the levels of these pro-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) of five COVID-19 patients in the intensive care unit, who were subjected to both inactivated SARS-CoV-2 and exosome therapy, with those of five healthy controls. The cytokine levels were quantified using the ELISA method. The collected data was analyzed in SPSS Version 26.0 and GraphPad Prism Version 9. According to the study findings, when PBMCs were exposed to inactivated SARS-CoV-2, pro-inflammatory cytokines increased in both patients and healthy controls. Notably, the cytokine levels were significantly elevated in the COVID-19 patients compared to the control group P-values were < 0.001, 0.001, 0.008, and 0.008 for TNF-α, IL-6, IL-17, and IFN-γ, respectively. Conversely, when both groups were exposed to exosomes, there was a marked reduction in the levels of pro-inflammatory cytokines. This suggests that exosome administration can effectively mitigate the hyperinflammation induced by COVID-19 by suppressing the production of pro-inflammatory cytokines in patients. These findings underscore the potential safety and efficacy of exosomes as a therapeutic strategy for COVID-19.

Expansion of Betatorquevirus and/or Gammatorquevirus in Patients with Severe Clinical Outcomes of the Liver Diseases.

Anellovirus (AV) is a ubiquitous virus in the human population. Individuals can be infected with multiple AV genera and species to form a heterogeneous repertoire, termed the anellome. Using advanced methods, we examined the anellomes from 12 paired serum and liver samples, as well as 2701 subjects with different clinical diagnoses. Overall, anellomes are remarkably individualized, with significant among-group differences (Kruskal-Wallis test p = 6.6 × 10-162 for richness and p = 7.48 × 10-162 for Shannon entropy). High dissimilarity scores (beta diversity) were observed between patient groups, except for paired serum and liver samples. At the population level, the relative abundance of combinational AV genus Betatorquevirus (torque teno mini viruses, TTMV), and Gammatorquevirus (torque teno midi viruses, TTMDV) exhibited an exponential distribution with a low bound point at 32%. Defined by this value, the AV TTMV/TTMDV-expanded anellome was significantly enriched among patients with acute liver failure (31.7%) and liver transplantation (40.7%), compared with other patient groups (χ2 test: p = 4.1 × 10-8-3.2 × 10-3). Therefore, anellome heterogeneity may be predictive of clinical outcomes in certain diseases, such as liver disease. The consistency of anellome between paired serum and liver samples indicates that a liquid biopsy approach would be suitable for longitudinal studies to clarify the causality of the AV TTMV/TTMDV-expanded anellome in the outcomes of liver disease.

Characterization of the Human Blood Virome in Iranian Multiple Transfused Patients.

Blood transfusion safety is an essential element of public health. Current blood screening strategies rely on targeted techniques that could miss unknown or unexpected pathogens. Recent studies have demonstrated the presence of a viral community (virobiota/virome) in the blood of healthy individuals. Here, we characterized the blood virome in patients frequently exposed to blood transfusion by using Illumina metagenomic sequencing. The virome of these patients was compared to viruses present in healthy blood donors. A total number of 155 beta-thalassemia, 149 hemodialysis, and 100 healthy blood donors were pooled with five samples per pool. Members of the Anelloviridae and Flaviviridae family were most frequently observed. Interestingly, samples of healthy blood donors harbored traces of potentially pathogenic viruses, including adeno-, rota-, and Merkel cell polyomavirus. Viruses of the Anelloviridae family were most abundant in the blood of hemodialysis patients and displayed a higher anellovirus richness. Pegiviruses (Flaviviridae) were only observed in patient populations. An overall trend of higher eukaryotic read abundance in both patient groups was observed. This might be associated with increased exposure through blood transfusion. Overall, the findings in this study demonstrated the presence of various viruses in the blood of Iranian multiple-transfused patients and healthy blood donors.

Gender disparity and temporal trend of liver cancer in China from 1990 to 2019 and predictions in a 25-year period.

Objective: This study aims to reveal epidemiological features and trends of liver cancer (LC) in China. Methods: We retrieved data from the Global Burden of Disease database 2019. Joinpoint regression was used to examine the temporal trend of LC. Future trends of LC were estimated using the Nordpred. Results: The incidence, mortality, and disability-standardized life year (DALY) rate of LC declined in China from 1990 to 2019. Among >210,000 LC cases in 2019, the LC incidences were nearly 3.15 times higher in males than in females. LC cases and LC-associated deaths were mostly found among patients aged 65 to 69 years. The proportion of LC attributable to hepatitis B decreased over time, whereas the proportions of LC attributable to hepatitis C, alcohol use, and non-alcoholic steatohepatitis increased modestly from 1990 to 2019. The majority of LC-associated deaths could be traced to four risk factors: smoking (20%), drug use (13.6%), alcohol use (11.7%), and high body mass index (10.1%). Based on the Nordpred prediction, there will be a steady decline in the incidence (39.0%) and mortality (38.3%) of liver cancer over a 25-year period from 2020 to 2044. Conclusion: The disease burden of liver cancer in China has declined over the past 30 years. However, it remains important to control liver cancer among high-risk populations, especially elderly males with obesity, alcohol use, tobacco use, and/or drug abuse.

Trends in the disease burden of HBV and HCV infection in China from 1990-2019.

OBJECTIVES: This study aimed to reveal the 30-year dynamics of hepatitis B virus (HBV) and hepatitis C virus (HCV) disease burden in China from 1990-2019. METHODS: HBV/HCV data were retrieved from the Global Burden of Disease database. Joinpoint regression was used to examine temporal trends. Age-period-cohort models were applied to evaluate effects of patient age, period, and cohort on HBV/HCV-associated mortality and incidences. RESULTS: A dramatic decrease in the disease burden of HBV was found from 1990-2019, but the disease burden of HCV has remained stable since 2000. Patient age, period, and cohort exerted a significant effect on the diseases burden of HBV and HCV infection. Compared with women, men had a higher risk of HBV/HCV infections as well as HBV/HCV-associated mortality and liver cancer. Overweight, alcohol, tobacco, and drug use were important risk factors associated with HBV/HCV-associated liver cancer. The incidences of HBV- and HCV-associated liver cancer from 2019-2044 are expected to decrease by 39.4% and 33.3%, respectively. CONCLUSION: The disease burden of HBV/HCV infection has decreased in China over the past 30 years, but HBV incidences remain high, especially in men. Effective management of HBV and HCV infections is still needed for high-risk populations.

Human gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection.

The SARS-CoV-2 pandemic has become one of the most serious health concerns globally. Although multiple vaccines have recently been approved for the prevention of coronavirus disease 2019 (COVID-19), an effective treatment is still lacking. Our knowledge of the pathogenicity of this virus is still incomplete. Studies have revealed that viral factors such as the viral load, duration of exposure to the virus, and viral mutations are important variables in COVID-19 outcome. Furthermore, host factors, including age, health condition, co-morbidities, and genetic background, might also be involved in clinical manifestations and infection outcome. This review focuses on the importance of variations in the host genetic background and pathogenesis of SARS-CoV-2. We will discuss the significance of polymorphisms in the ACE-2, TMPRSS2, vitamin D receptor, vitamin D binding protein, CD147, glucose-regulated protein 78 kDa, dipeptidyl peptidase-4 (DPP4), neuropilin-1, heme oxygenase, apolipoprotein L1, vitamin K epoxide reductase complex 1 (VKORC1), and immune system genes for the clinical outcome of COVID-19.

Molecular epidemiology, phylogenetic analysis and genotype distribution of hepatitis B virus in Saudi Arabia: Predominance of genotype D1.

Despite the implementation of various vaccination programs, hepatitis B virus (HBV) poses a considerable health problem in Saudi Arabia. Insight on HBV evolutionary history in the region is limited. We performed a comprehensive epidemiological and phylogenetic reconstruction based on a large cohort of HBV infected patients. Three hundred and nineteen HBV-infected patients with different clinical manifestations, including inactive and active chronic carriers and patients with cirrhosis and hepatocellular carcinoma (HCC), were enrolled in this study. The full-length large S gene was amplified and sequenced. Phylogenetic analysis was performed to determine the genotype and subgenotypes of the isolates. Phylogenetic tree analysis revealed that genotype D is the most dominant genotype among patients. Moreover, this analysis identified two strains with genotype E isolated from active carriers. Detailed phylogenetic analyses confirmed the presence of four HBV D subgenotypes, D1 (93%, n = 296), D2 (0.02%, n = 5), D3 (0.003%, n = 1), and D4 (0.003%, n = 1). In addition, six genotype D strains were not assigned to any existing HBV D subgenotype. The large S gene of eight strains showed signatures of genotype recombination between the genotypes D and A and between D and E. Several strains harbored medically important point mutations at the protein level. Along with the dominance of the HBV genotype D, isolation of the E genotype and several recombinant strains from patients with Saudi Arabian origin is an essential result for decisions involving therapeutic measures for patients. Development of vaccines and detection of diagnostic escape mutations at antigenic epitopes on the HBsAg will be valuable to public health authorities. Furthermore, the diversity at the nucleotide and amino acid levels and different proportions of dN/dS at the PreS1, PreS2, and HBsAg reveal the selective pressure trend from inactive status towards advanced liver diseases.

Mass migration to Europe: an opportunity for elimination of hepatitis B virus?

People from low-to-middle income countries have been migrating to western Europe on a large scale in recent years. Data indicate that the number of first-time asylum applications by non-EU members increased from 290 000 in 2011 to more than 1·3 million in 2015. During the peak period of migration, The Global Health Sector Strategy on Viral Hepatitis was adopted by WHO. Viral hepatitis, and particularly hepatitis B virus (HBV), is an important disease because of its high prevalence and associated mortality. In some cases, HBV can be carried by refugees arriving from regions of high and intermediate prevalence. Refugees with HBV might not show clinical symptoms and not be diagnosed in destination countries with a low prevalence, where screening is not regularly done. Although transmission to the host population is low, dedicated surveillance and tailored public health policies are required. It is important to note that some of the countries that receive many migrants do not have a universal HBV vaccination programme. In this Viewpoint, we argue that the current large-scale movement from regions with high or intermediate HBV prevalence should be taken as an opportunity to achieve viral hepatitis elimination targets, by establishing a well prepared infrastructure for HBV screening, vaccination, and treatment.

Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development.

CONTEXT: After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%. EVIDENCE ACQUISITION: All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection. RESULTS: The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence. CONCLUSIONS: Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity.

Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions.

The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.