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:Three years after the pandemic, we still have an imprecise comprehension of the pathogen landscape and we are left with an urgent need for early detection methods and effective therapy for severe COVID-19 patients. The implications of infection go beyond pulmonary damage since the virus hijacks the host's cellular machinery and consumes its resources. Here, we profiled the plasma proteome and metabolome of a cohort of 57 control and severe COVID-19 cases using high-resolution mass spectrometry. We analyzed their proteome and metabolome profiles with multiple depths and methodologies as conventional single omics analysis and other multi-omics integrative methods to obtain the most comprehensive method that portrays an in-depth molecular landscape of the disease. Our findings revealed that integrating the knowledge-based and statistical-based techniques (knowledge-statistical network) outperformed other methods not only on the pathway detection level but even on the number of features detected within pathways. The versatile usage of this approach could provide us with a better understanding of the molecular mechanisms behind any biological system and provide multi-dimensional therapeutic solutions by simultaneously targeting more than one pathogenic factor.
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: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.
Project description:The adult data set. The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. A multiomics approach identified alterations in analytes associated with fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults.
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global health crisis, particularly affecting the elderly, who are more susceptible to severe outcomes. However, 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. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labeling. We analyzed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 can be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades.