Multi-omic approach identifies a transcriptional network coupling innate immune response to proliferation in the blood of COVID-19 cancer patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA691231 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer for which mortality rate in cancer patients affected by COVID-19 is elevated. SARS-CoV-2 infection is known to alter immune system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes has been so far poorly investigated. We conducted a multi-omic analysis of immunological parameters in COVID-19 patients with and without cancer. We found that 8 pro-inflammatory factors out of 27 analysed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8+ T, CD4+ T central memory, Mucosal associated invariant T cells (MAIT) NKT and T cells were reduced while B memory cells, plasmablasts, late NK and plasmacytoid dendritic cells were expanded in COVID-19 cancer patients. A 19 gene expression signature of peripheral blood cells was able to discriminate COVID-19 cancer and without cancer patients. Gene set enrichment analysis highlights an increased gene expression in Interferon response and signalling which paired with aberrant cell cycle regulation in cancer patients. Ten out of these 19 genes were specific of COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients that might contribute to decipher their higher frequency of severe events. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients. This might also lead to design of novel therapeutic strategies for COVID-19 cancer patients.
2021-11-10 | GSE164571 | GEO
Project description:This study utilizes multi-omic biological data to perform deep immunophenotyping on the major immune cell classes in COVID-19 patients. 10X Genomics Chromium Single Cell Kits were used with Biolegend TotalSeq-C human antibodies to gather single-cell transcriptomic, surface protein, and TCR/BCR sequence information from 254 COVID-19 blood draws (a draw near diagnosis (-BL) and a draw a few days later (-AC)) and 16 healthy donors.
2020-10-29 | E-MTAB-9357 | biostudies-arrayexpress
Project description:Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
2021-05-08 | GSE174072 | GEO
Project description:Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
| PRJNA728100 | ENA
Project description:Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer leading to elevated mortality rates. SARS-CoV-2 infection is known to alter immune system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes have so far been poorly investigated. We conducted a multi-omic analysis of immunological parameters in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with and without cancer. Healthy donors and SARS-CoV-2-negative cancer patients were also included as controls. At the infection peak, cytokine multiplex analysis of blood samples, cytometry by time of flight (CyTOF) cell population analyses, and Nanostring gene expression using Pancancer array on PBMCs were performed. We found that eight pro-inflammatory factors (IL-6, IL-8, IL-13, IL-1ra, MIP-1a, IP-10) out of 27 analyzed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8+T, CD4+T central memory, Mucosal-associated invariant T (MAIT), natural killer (NK), and γδ T cells were reduced, while B plasmablasts were expanded in COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients. A 19-gene expression signature of PBMCs is able to discriminate COVID-19 patients with and without solid cancers. Gene set enrichment analysis highlights an increased gene expression linked to Interferon α, γ, α/β response and signaling which paired with aberrant cell cycle regulation in cancer patients. Ten out of the 19 genes, validated in a real-world consecutive cohort, were specific of COVID-19 cancer patients independently from different cancer types and stages of the diseases, and useful to stratify patients in a COVID-19 disease severity-manner. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients.
| S-EPMC8553595 | biostudies-literature
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.
2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress
Project description:Using RNA-seq and high-resolution mass spectrometry we performed a comprehensive systems analysis on 128 plasma and leukocyte samples from hospitalized patients with or without COVID-19 (n=102 and 26 respectively) and with differing degrees of disease severity. We generated abundance measurements for over 17,000 transcripts, proteins, metabolites, and lipids and compiled them with clinical data into a curated relational database. This resource offers the unique opportunity to perform systems analysis and cross-ome correlations to both molecules and patient outcomes. In total 219 molecular features were mapped with high significance to COVID-19 status and severity, including those involved in processes such as complement system activation, dysregulated lipid transport, and B cell activation. In one example, we detected a trio of covarying molecules – citrate, plasmenyl-phosphatidylcholines, and gelsolin (GSN) – that offer both pathophysiological insight and potential novel therapeutic targets. Further, our data revealed in some cases, and supported in others, that several biological processes were dysregulated in COVID-19 patients including vessel damage, platelet activation and degranulation, blood coagulation, and acute phase response. For example, we observed that the coagulation-related protein, cellular fibronectin (cFN), was highly increased within COVID-19 patients and provide new evidence that the upregulated proteoform stems from endothelial cells, consistent with endothelial injury as a major activator of the coagulation cascade. The abundance of prothrombin, which is cleaved to form thrombin during clotting, was significantly reduced and correlated with severity and might help to explain the hyper coagulative environment of SARS-CoV-2 infection. From transcriptomic analysis of leukocytes, we concluded that COVID-19 patients with acute respiratory distress syndrome (ARDS) demonstrated a phenotype that overlapped with, but was distinct from, that found in patients with non-COVID-19-ARDS. To aid in the global efforts toward elucidation of disease pathophysiology and therapeutic development, we created a web-based tool with interactive visualizations allowing for easy navigation of this systems-level compendium of biomolecule abundance in relation to COVID-19 status and severity. Finally, we leveraged these multi-omic data to predict COVID-19 patient outcomes with machine learning, which highlighted the predictive power of these expansive molecular measurements beyond the standardized clinical estimate of 10-year survival Charlson score.
2020-08-29 | GSE157103 | GEO
Project description:Large-scale Multi-omic Analysis of COVID-19 Severity
| PRJNA660067 | ENA
Project description:At this stage in the COVID-19 pandemic, most infections are 'breakthrough' infections that occur in individuals with prior immunity to SARS-CoV-2 through infection or vaccination. Understanding both innate and adaptive immune induction in the setting of breakthrough infection is critical to refining vaccine strategies to ensure long-term efficacy against emerging variants, yet existing studies have primarily focused on adaptive immune responses. Here, we performed single-cell transcriptomic, proteomic, and functional profiling of innate and adaptive immunity during primary and breakthrough COVID-19 infections by comparing immune responses between unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave. Breakthrough infections were characterized by a significantly less activated transcriptomic profile in CD56dim NK cells and monocytes, with induction of pathways limiting NK cell proliferation and monocyte migratory potential. Furthermore, we observed a female-specific trend of increased transcriptomic activation of CD16+ monocytes and type-2 conventional dendritic cells (cDC2s) during breakthrough infections. Despite these differences, antibody-dependent cellular cytotoxicity responses were similar between breakthrough and primary infection groups. These insights suggest that prior vaccination prevents overactivation of innate immune responses during breakthrough infections with discernible sex-specific patterns and underscore the potential of harnessing vaccines in mitigating pathologic immune responses resulting from overactivation.
2025-01-30 | GSE261862 | GEO
Project description:Risk of severe disease and death due to coronavirus 2019 (COVID-19) is increased in certain patient demographic groups, including those who are of advanced age, male sex, and obese body mass index. Investigations of the biological variations that contribute to this risk have been hampered by heterogeneous severity, with immunologic features of critical disease potentially obscuring differences between risk groups. To examine immune heterogeneity related to demographic risk factors, we enrolled 38 patients hospitalized with clinically homogeneous COVID-19 pneumonia – defined as oxygen saturation <94% on room air without respiratory failure, septic shock, or multiple organ dysfunction – and performed single-cell RNA-sequencing of leukocytes collected at admission. Examination of individual risk factors identified strong shifts within neutrophil and monocyte/dendritic cell compartments, revealing altered immune cell type-specific responses in higher-risk COVID-19 patient subgroups. Specifically, we found transcriptional evidence of altered neutrophil maturation in aged versus young patients and enhanced cytokine responses in monocytes/dendritic cells of male versus female patients. Such innate immune cell alterations may contribute to outcome differences linked to these risk factors. They also highlight the importance of diverse patient cohorts in studies of therapies targeting the immune response in COVID-19.
2023-10-11 | GSE236177 | GEO