Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection

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 an...

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Veröffentlicht in:Nature communications Jg. 11; H. 1; S. 6319 - 15
Hauptverfasser: Desai, Niyati, Neyaz, Azfar, Szabolcs, Annamaria, Shih, Angela R., Chen, Jonathan H., Thapar, Vishal, Nieman, Linda T., Solovyov, Alexander, Mehta, Arnav, Lieb, David J., Kulkarni, Anupriya S., Jaicks, Christopher, Xu, Katherine H., Raabe, Michael J., Pinto, Christopher J., Juric, Dejan, Chebib, Ivan, Colvin, Robert B., Kim, Arthur Y., Monroe, Robert, Warren, Sarah E., Danaher, Patrick, Reeves, Jason W., Gong, Jingjing, Rueckert, Erroll H., Greenbaum, Benjamin D., Hacohen, Nir, Lagana, Stephen M., Rivera, Miguel N., Sholl, Lynette M., Stone, James R., Ting, David T., Deshpande, Vikram
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 09.12.2020
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ISSN:2041-1723, 2041-1723
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Abstract 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. Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.
AbstractList 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.Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.
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.
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.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.
Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.
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. Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.
ArticleNumber 6319
Author Warren, Sarah E.
Neyaz, Azfar
Rivera, Miguel N.
Rueckert, Erroll H.
Szabolcs, Annamaria
Shih, Angela R.
Mehta, Arnav
Jaicks, Christopher
Reeves, Jason W.
Colvin, Robert B.
Monroe, Robert
Ting, David T.
Greenbaum, Benjamin D.
Raabe, Michael J.
Juric, Dejan
Nieman, Linda T.
Stone, James R.
Chen, Jonathan H.
Solovyov, Alexander
Lieb, David J.
Pinto, Christopher J.
Thapar, Vishal
Kim, Arthur Y.
Lagana, Stephen M.
Sholl, Lynette M.
Deshpande, Vikram
Chebib, Ivan
Hacohen, Nir
Kulkarni, Anupriya S.
Danaher, Patrick
Gong, Jingjing
Xu, Katherine H.
Desai, Niyati
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  organization: The Broad Institute
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  organization: Massachusetts General Hospital Cancer Center
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  organization: Department of Medicine, Massachusetts General Hospital
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  organization: Massachusetts General Hospital Cancer Center, Department of Pathology, Massachusetts General Hospital
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33298930$$D View this record in MEDLINE/PubMed
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Copyright_xml – notice: The Author(s) 2020
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– reference: 32766600 - medRxiv. 2020 Aug 02;:
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Snippet 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...
Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be...
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Adult
Aged
Aged, 80 and over
Aspartic Acid Endopeptidases - metabolism
Autopsies
Autopsy
Cadavers
COVID-19
COVID-19 - immunology
COVID-19 - metabolism
Damage
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - pathology
Epithelial Cells - virology
Female
Fibrosis
Gene expression
Genes
Heterogeneity
Host Microbial Interactions
Humanities and Social Sciences
Humans
Immunity
Immunohistochemistry
In Situ Hybridization
Infections
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Interferons - metabolism
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Lung - virology
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Macrophages - immunology
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Mucins - genetics
Mucins - metabolism
multidisciplinary
Patients
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Spatial heterogeneity
Surface-Active Agents - metabolism
Transcription activation
Transcriptome
Viral diseases
Viral Load
Viruses
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Title Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection
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