BackgroundThe immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential.Methods100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed.ResultsWe found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844.ConclusionThe present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.

ObjectiveTo investigate the influence of nonalcoholic fatty liver disease (NAFLD) on the antiviral response of patients with chronic hepatitis B (CHB), and to provide a reference for clinical treatment of such patients. MethodsA total of 187 patients who attended Shenzhen Third People’s Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients, NAFLD group with 41 patients, and CHB+NAFLD group with 103 patients. Related indices were measured at enrollment different time points of follow-up, including body height, body weight, alanine aminotransferase (ALT), aspartate aminotransferase, four blood lipid parameters, four indicators of liver fibrosis, aspartate aminotransferase-to-platelet ratio index, HBsAg, HBeAg, anti-HBe, and HBV DNA quantification, and the CHB patients and the CHB+NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12, 24, 48, 72, and 96 of antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. ResultsCompared with the NAFLD group at baseline, the CHB group and the CHB+NAFLD group had significantly lower platelet count, ALT, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, and right lobe of liver oblique diameter (all P＜0.05), and compared with the CHB group, the CHB+NAFLD group had significantly higher body mass index, total cholesterol, and triglyceride and a significantly lower spleen thickness (all P＜0.05), while there were no significant differences in the other indicators between the two groups at baseline (all P＞0.05). At week 12 of antiviral therapy, there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB+NAFLD group (all P＞0.05); compared with the CHB+NAFLD group at weeks 24 and 48, the CHB group had significantly greater reductions in ALT (Z=-2.128 and -3.055, both P＜0.05) and GGT (Z=-2.025 and -1.631, both P＜0.05); at week 48, the CHB group and the CHB+NAFLD group had a significant reduction in HBV DNA (Z=-6.445 and -4.415, both P＜0.001), and the CHB group had a significantly greater reduction. The CHB+NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy (χ2=14.237, 13.961, 15.226, 10.462, and 13.030, all P＜0.05). At week 48 of antiviral therapy, the CHB+NAFLD group had a significantly lower HBeAg clearance rate than the CHB group (χ2=5.309, P=0.021), while there was no significant difference between the two groups at week 96 (χ2=0.117, P=0.732). At weeks 24, 48, 72, and 96 of antiviral therapy, the CHB+NAFLD group had a significantly lower ALT normalization rate than the CHB group (χ2=12.049, 5.287, 11.407, and 11.375, all P＜0.05). ConclusionNAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy.

We performed our sequencing and analysis in CapitalBio Technology (Beijing, China). A549 cells were infected with SARS-CoV-2, panH1N1 and H7N9 at a MOI of 0.01 for 60 hr. Total RNAs from control and virus infected cells were extracted using the TRIzol reagent according to the manufacturer’s instructions (Invitrogen, USA). The genomic DNA was removed using DNase I (Takara, Japan). RNA samples were assessed for their quality using the RNA 6000 pico kit (Agilent, USA) and quantified using the ND-2000 (NanoDrop Technologies). Only the high quality RNA was selected to construct the sequencing library with the Illumina TruSeq Stranded mRNA Library Preparation kit (Illumina, USA). The NEBNext Multiplex Small RNA Library Prep Set for Illumina (NEB, USA) was used for RNA library preparation.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) at the end of 2019 has caused a large global outbreak and now become a major public health issue. However, there is currently a lack of data underlying how the human host interacts with SARS-CoV-2 virus. In the current study, We performed Venn-analysis, Gene ontology (GO), KEGG pathway analysis and Protein-protein interaction analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during human respiratory tract cell infection with SARS-CoV-2. We found 36 overlapping upregulated genes among different types of cells after viral infection. Further functional enrichment analysis revealed these Differential Expressed Genes (DEGs) are most likely involved in biological processes related to inflammatory response and response to cytokine, cell component related to extracellular space and I-kappa B/NF-kappa B complex, molecular function related to protein binding and cytokine activity. KEGG pathways analysis highlighted altered conical and casual pathways related to TNF, NF-kappa B, Cytokine-cytokine receptor interaction and IL-17 signaling pathways during SARS CoV-2 infection with CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, IL32, CX3CL1, CCL20, IRF1, NFKB2 and NFKB1A up-regulated which may explain the inflammatory cytokine storms associated with severe cases of COVID-19.

Abstract Background Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis. Methods This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established. Results Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0–30, 31–60, 61–90, 91–120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups. Conclusions Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

Importance Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.