Reduction of ACE2 serum concentrations by telbivudine in chronic hepatitis B patients.

BACKGROUND: Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has wreaked havoc worldwide since December 2019. Currently, no effective medical treatments have been approved. As the epidemic continues to spread, SARS-CoV-2 mutants emerge, some of which become more infectious with increasing vaccine resistance. The main route for SARS-CoV-2 to enter the host cells is by binding of its spike protein to the host receptor, angiotensin-converting enzyme 2 (ACE2). Besides the membrane-bound form of ACE2, the soluble form of ACE2 (sACE2) can also bind SARS-CoV-2 for viral endocytosis. OBJECTIVE: Previously, we found that telbivudine reduced the concentrations of ACE1 in blood. Therefore, we speculated that this drug might also reduce the concentrations of sACE2. METHODS: In this retrospective study, serum samples from 39 hepatitis B patients receiving telbivudine were collected and examined for sACE2 concentrations using an ELISA kit. RESULTS: It was found that the serum concentrations of sACE2 were significantly declined in chronic hepatitis B patients treated by telbivudine. CONCLUSION: Telbivudine treatment reduced sACE2 concentrations, which could potentially reduce the infection risk of SARS-CoV-2.

Risk of Herpes Zoster in Patients with Pulmonary Tuberculosis-A Population-Based Cohort Study.

BACKGROUND: Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. METHODS: This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. RESULTS: A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. CONCLUSION: Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.

Etanercept Ameliorates Cardiac Fibrosis in Rats with Diet-Induced Obesity.

Diet-induced obesity (DIO) is considered the main risk factor for cardiovascular diseases. Increases in the plasma levels of tumor necrosis factor alpha (TNF-α) is associated with DIO. Etanercept, a TNF-α inhibitor, has been shown to alleviate cardiac hypertrophy. To investigate the effect of etanercept on cardiac fibrosis in DIO model, rats on high fat diet (HFD) were subdivided into two groups: the etanercept group and vehicle group. Cardiac injury was identified by classic methods, while fibrosis was characterized by histological analysis of the hearts. Etanercept treatment at 0.8 mg/kg/week twice weekly by subcutaneous injection effectively alleviates the cardiac fibrosis in HFD-fed rats. STAT3 activation seems to be induced in parallel with fibrosis-related gene expression in the hearts of HFD-fed rats. Decreased STAT3 activation plays a role in the etanercept-treated animals. Moreover, fibrosis-related genes are activated by palmitate in parallel with STAT3 activation in H9c2 cells. Etanercept may inhibit the effects of palmitate, but it is less effective than a direct inhibitor of STAT3. Direct inhibition of STAT3 activation by etanercept seems unlikely. Etanercept has the ability to ameliorate cardiac fibrosis through reduction of STAT3 activation after the inhibition of TNF-α and/or its receptor.

Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections (preprint)

Importance: Vaccine breakthrough by an emergent SARS-CoV-2 variant poses a great risk to global public health. Objective: To determine the SARS-CoV-2 variant responsible for 6 cases of vaccine breakthrough. Design: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 by qPCR for Wuhan-Hu1 and Alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. Setting: Transmission event occurred at events surrounding a wedding outside of Houston, TX. Two patients from India, likely transmitted the Delta variant to other guests. Participants: Following a positive SARS-CoV-2 qPCR test at a third-party site, six fully vaccinated patients were investigated. Three males and three females ranged from 53 to 69 years old. One patient suffered from diabetes while three others were classified as overweight. No significant other comorbidities were identified. None of the patients had a history of failed vaccination.

Oligonucleotide Capture Sequencing of the SARS-CoV-2 Genome and Subgenomic Fragments from COVID-19 Individuals (preprint)

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.

Oligonucleotide capture sequencing of the SARS-CoV-2 genome and subgenomic fragments from COVID-19 individuals (preprint)

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.