While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16−natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+and CD8+T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.
The pandemic outbreak of the 2019 coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading rapidly and poses a great threat to human health. As such, developing rapid and accurate immunodiagnostic methods for the identification of infected persons is needed. Here, we proposed a simple but sensitive on-site testing method based on spike protein-conjugated quantum dot (QD) nanotag-integrated lateral flow immunoassay (LFA) to simultaneously detect SARS-CoV-2-specific IgM and IgG in human serum. Advanced silica-core@dual QD-shell nanocomposites (SiO2@DQD) with superior luminescence and stability were prepared to serve as fluorescent nanotags in the LFA strip and guarantee high sensitivity and reliability of the assay. The performance of the SiO2@DQD-strip was fully optimized and confirmed by using 10 positive serum samples from COVID-19 patients and 10 negative samples from patients with other respiratory diseases. The practical clinical value of the assay was further evaluated by testing 316 serum samples (114 positive and 202 negative samples). The overall detection sensitivity and specificity reached 97.37% (111/114) and 95.54% (193/202), respectively, indicating the huge potential of our proposed method for the rapid and accurate detection of SARS-CoV-2-infected persons and asymptomatic carriers.
Objective: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent hepatitis B virus (HBV) mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the 2 regimens are lacking. Design: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to 31 March 2024 and extracted data from cohort studies and randomized controlled trials (RCTs) in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. Results: We included 31 studies with 2588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6–12 months (risk ratio: 0.10, 95% confidence interval [CI] .07–.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval .16–7.61). Network meta-analysis showed equal efficacy of the 2 regimens in reducing MTCT (risk ratio: 1.09, 95% CI .15–7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: .77 vs .72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. Conclusions: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.
Objective: To elucidate the regional distribution of metabolic dysfunction‐associated steatohepatitis (MASH) fibrosis within the liver and to identify potential therapeutic targets for MASH fibrosis. Methods: Liver sections from healthy controls, patients with simple steatosis and MASH patients were analysed using spatial transcriptomics integrated with single‐cell RNA‐seq. Results: Spatial transcriptomics analysis of liver tissues revealed that the fibrotic region (Cluster 9) was primarily distributed in lobules, with some fibrosis also found in the surrounding area. Integration of the single‐cell‐sequencing data set (GSE189175) showed a greater proportion of inflammatory cells (Kupffer cells and T cells) and myofibroblasts in MASH. Six genes, showing high‐ or low‐specific expression in Cluster 9, namely, ADAMTSL2, PTGDS, S100A6, PPP1R1A, ASS1 and G6PC, were identified in combination with pathology. The average expression levels of ADAMTSL2, PTGDS and S100A6 on the pathological HE staining map were positively correlated with the increase in the degree of fibrosis and aligned strongly with the distribution of fibrosis. ADAMTSL2+ myofibroblasts play a role in TNF signalling pathways and in the production of ECM structural components. Pseudotime analysis indicated that in the early stages of MASH, infiltration by T cells and Kupffer cells triggers a significant inflammatory response. Subsequently, this inflammation leads to the activation of hepatic stellate cells (HSCs), transforming them into myofibroblasts and promoting the development of liver fibrosis. Conclusion: This study is the first to characterise lineage‐specific changes in gene expression, subpopulation composition, and pseudotime analysis in MASH fibrosis and reveals potential therapeutic targets for this condition.