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Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation [NanoString GeoMx]

ABSTRACT: To delineate the in situ immune responses to SARS-CoV-2 viral infection, we performed comprehensive immune profiling in COVID-19 decedents. In this study, we described the immune microenvironment of COVID-19 patients through transcriptome sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182920 | GEO | 2021/11/21

REPOSITORIES: GEO

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Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation [RNA-seq]

Project description:To delineate the in situ immune responses to SARS-CoV-2 viral infection, we performed comprehensive immune profiling in COVID-19 decedents. In this study, we described the immune microenvironment of COVID-19 patients through transcriptome sequencing.

2021-11-21 | GSE182917 | GEO

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation [NanoString GeoMx]

Project description:Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation [NanoString GeoMx]

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Single Nuclei RNA Sequencing Analysis of Cardiac Microthrombi in Fatal Covid-19

Project description:Cardiac microthrombi have been variably identified at autopsy of Covid-19 decedents. Little is known about the morphologic and molecular changes associated with cardiac microthrombi and whether predictive biomarkers exist. We sought to determine the prevalence, pathogenesis, and biomarker risk factors of Covid-19-associated cardiac microthrombi. In addition to histology and immunohistochemical analyses, we investigated right verticles from 8 Covid-19 decedents via single nuclei RNA sequencing for cell-type specific transcriptional differences between hearts with and without microthrombi, as well as between Covid-19 decedents and publicly available non-Covid-19 donor controls.

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Nanostring GeoMx digital spatial profliing of myeloid cells from COVID-19 and normal lung

Project description:To determine definitively whether lung myeloid cells exhibit a pro- or anti-inflammatory signature in COVID-19 disease, we performed digital spatial profiling using the nanoString GeoMx ImmuneOncology plus COVID-19 platform on CD68+ macrophages, myeloperoxidase+ granulocytes and cytokeratin+ epithelium in normal and COVID-19 lung tissue specimens, collecting RNA expression data for each type within 6-8 regions of 5mM tissue sections. One COVID-19 lung tissue yielded minimal sequence data and was excluded from analysis. A volcano plot and heat map of differentially expressed genes within macrophages demonstrate that COVID-19 lung macrophages when compared with normal lung macrophages exhibit a largely alternatively activated, wound-healing signature characterized by expression of the alternatively active macrophage marker CD163, complement/coagulation genes (C1QA, C1QB, THBS1, C1S, C1R), IL6 signaling (STAT2, STAT1) and wound healing (COL3A1, COL6A3), but also interferon response signatures (ISG15, OAS3, IFITM2, IFI6, HLA-A, HLA-B, HLA-C) (Fig. 3H-J). As one of the tissues used for macrophage spatial profiling was from a patient was positive for the virus at the time of death, we compared the expression profiles of virus+ and virus- specimens and found that macrophages in virus+ tissues predominantly expressed an interferon-associated signature

2023-04-12 | GSE190494 | GEO

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation [RNA-seq]

Project description:Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation [RNA-seq]

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Multi-omic analysis resolves coordinated immune responses to mild, moderate and severe COVID-19

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

Columbia University/NYP COVID-19 Lung Atlas

Project description:We profiled 116,314 cells using snRNA-seq of 20 frozen lungs obtained from 19 COVID-19 decedents and seven control patients with short postmortem interval (PMI) autopsies. The COVID-19 cohort comprises seven female and 12 male decedents, including 13 patients of Hispanic ethnicity, with an age range from 58 to >89 years who had acquired SARS-CoV-2 infection and succumbed to the disease. The average time from symptom onset to death was 27.5 days (range, 4–63 days). After rapid autopsy with a median PMI of 4 hours (range 2–9 hours) collected tissues were either flash-frozen or frozen following OCT (optimal cutting temperature) embedment and subjected to snRNA-seq using a droplet-based platform (10x Genomics). All included patients had underlying hypertensive disorder and frequently one or more additional co-morbidities associated with increased risk for severe COVID-19.

2021-04-29 | GSE171524 | GEO

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

Project description:While critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during COVID-19 ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using scRNA-seq and plasma proteomics, we discovered that compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin (PG) signalling. Dexamethasone during severe COVID-19 depleted circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated gene, and activated IL1R2+ve neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils, preferential steroid-induced immature neutrophil expansion, and possibly different effects on outcome. Our single-cell atlas (www.biernaskielab.ca/COVID_neutrophil) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.

2021-10-05 | GSE157789 | GEO

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.

Project description: Not available

| S-EPMC8755743 | biostudies-literature

A single-cell atlas of the peripheral immune response to severe COVID-19

Project description:There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2 which has infected more than 3 million people worldwide. Approximately 20% of patients with COVID-19 develop severe disease and 5% require intensive care. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines that may be produced by a subset of inflammatory monocytes, lymphopenia, and T cell exhaustion. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from 7 patients hospitalized for COVID-19 and 6 healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19. Sample IDs used in the manuscript were shortened for clarity. They relate to the titles of deposited files as follows: covid_555_1: C1 A covid_555_2: C1 B covid_556: C2 covid_557: C3 covid_558: C4 covid_559: C5 covid_561: C7 HIP002: H1 HIP015: H2 HIP023: H3 HIP043: H4 HIP044: H5 HIP045: H6

2020-05-18 | GSE150728 | GEO

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