Project description:To trace immune responses in COVID-19 patients with severity, we performed in-depth, longitudinal single-cell multiomics involving T-cell receptor (TCR)/B-cell receptor (BCR) sequencing, feature barcoded antibody (Ab) panel detection (i.e., cellular indexing of transcriptomes and epitopes by sequencing, CITE-seq) followed by RNA sequencing in a single-cell resolution.
Project description:Definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain confused. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform.
Project description:The unique pulmonary pathophysiology of COVID-19 compared with other respiratory viral infections remains poorly understood. We performed integrative bulk and single-cell RNA sequencing on bronchoalveolar lavage fluid (BALF) from patients with COVID-19 (n=24) or influenza (n=10) and healthy controls (n=10). While influenza primarily induced conventional inflammatory responses, COVID-19 triggered distinct microenvironmental remodeling characterized by a specific cilium-related gene signature (e.g., DNAH9, FOXJ1) and expansion of ciliated and airway epithelial cells. Cross-tissue comparison with peripheral blood mononuclear cells uncovered a compartmentalized immune response, particularly for Lipocalin-2 (LCN2), which showed opposite expression trends between the lung and systemic circulation. This study identifies ciliary dysfunction and epithelial-immune crosstalk as key features distinguishing COVID-19 from influenza and highlights epithelial-derived LCN2 as a robust, compartmentalized biomarker for disease severity.
Project description:The unique pulmonary pathophysiology of COVID-19 compared with other respiratory viral infections remains poorly understood. We performed integrative bulk and single-cell RNA sequencing on bronchoalveolar lavage fluid (BALF) from patients with COVID-19 (n=24) or influenza (n=10) and healthy controls (n=10). While influenza primarily induced conventional inflammatory responses, COVID-19 triggered distinct microenvironmental remodeling characterized by a specific cilium-related gene signature (e.g., DNAH9, FOXJ1) and expansion of ciliated and airway epithelial cells. Cross-tissue comparison with peripheral blood mononuclear cells uncovered a compartmentalized immune response, particularly for Lipocalin-2 (LCN2), which showed opposite expression trends between the lung and systemic circulation. This study identifies ciliary dysfunction and epithelial-immune crosstalk as key features distinguishing COVID-19 from influenza and highlights epithelial-derived LCN2 as a robust, compartmentalized biomarker for disease severity.
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.