Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Severe acute respiratory syndrome coronavirus 2 Homo sapiens
PROVIDER: GSE159788 | GEO | 2020/11/01
REPOSITORIES: GEO
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Project description:The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.
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Project description:The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.
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Project description:The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed specimens from 24 autopsies from patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the intra-pulmonary spatial heterogeneity of the virus corresponded to focal expression of interferon response genes and association with immune checkpoint genes In this dataset, we capture the GeoMx DSP RNA profiling work done in conjunction with this study. The files here represent SARS-CoV-2 infected rapid autopsy patients (n = 6) which were profiled with the NanoString GeoMx COVID19 Atlas RNA panel v1.0. This panel was then read out using Illumina sequencing following standard library preparation according to manufacturer protocols. Attached below are low-resolution images of each slide with placement of all ROIs, as well as individual images of each ROI, segments, and UV illuminated IF channels. For access to high resolution (single channel, composite, or ROI) images please contact GeoMxSupport@nanostring.com or the corresponding author of the study. RNA sequencing data and results for bulk RNA profiling can be accessed in study GSE150316.
2020-11-14 | GSE159787 | GEO
Project description:The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed specimens from 24 autopsies from patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the intra-pulmonary spatial heterogeneity of the virus corresponded to focal expression of interferon response genes and association with immune checkpoint genes In this dataset, we capture the GeoMx DSP protein profiling work done in conjunction with this study. The files here represent SARS-CoV-2 infected rapid autopsy patients (n = 6) which were profiled with the following nanoString GeoMx protein panels: Immune Cell Profiling Core v1.0, IO Drug Target Module v1.0, Immune Cell Typing Module v1.0, Immune Activation Status Module v1.0, PI3K/AKT Signaling Module v1.0, MAPK Signaling Module v0.9, and Cell Death Module v0.9. These panels were then read out using Nanostring nCounter quantification following standard HybCode panel profiling protocols. For access to high resolution (single channel, composite, or ROI) images please contact the corresponding author or GeoMxSupport@nanostring.com. RNA sequencing data and results for bulk RNA profiling can be accessed in study GSE150316.
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Project description:Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection
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