Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures

Margaroli, Camilla; Benson, Paul; Sharma, Nirmal; Madison, Matthew C.; Robison, Sarah; Arora, Nitin; Ton, Kathy; Liang, Yan; Zhang, Liang; Patel, Rakesh P.; Gaggar, Amit

doi:10.1016/j.xcrm.2021.100242

Cited by 45 publications

(52 citation statements)

References 43 publications

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“…The unique phenotype of COVID-related lung injury was confirmed by Margaroli et al [28], who, by means of a spatial transcriptomic platform on autopsy-derived lung tissue, documented a more firboproliferative response of SARS-COV-2 infection versus H1N1. Overall, due to the distint fibrotic and prothrombotic ARDS phenotype of COVID-19, pulmonary vasculature is largely affected, being responsible for the increased RV afterload, and therefore possibly contributing to RV alterations especially in severe COVID-related ARDS.…”

Section: Resultsmentioning

confidence: 74%

Persistent Right Ventricle Dilatation in SARS-CoV-2–Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support

Lazzeri

Bonizzoli

Batacchi

et al. 2022

Journal of Cardiothoracic and Vascular Anesthesia

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Resultsmentioning

confidence: 74%

Persistent Right Ventricle Dilatation in SARS-CoV-2–Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support

Lazzeri

Bonizzoli

Batacchi

et al. 2022

Journal of Cardiothoracic and Vascular Anesthesia

View full text Add to dashboard Cite

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“…Note: red font: upregulation, blue font: downregulation in this study. Studies compared include Margaroli et al 2021 [ 41 ], Grant et al 2021 [ 42 ], Desai et al 2020 [ 43 ] and Butler et al 2021 [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures

et al. 2021

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies. Here, we use targeted transcriptomics of FFPE tissue using the Nanostring GeoMX™ platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients. Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza. Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.

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“…Several studies have reported massive immune cell infiltration in the lungs during severe COVID-19, indicative of severe COVID-19 as a manifestation of a hyperinflammatory state in which the maladaptive immune response itself can cause lung issue injury. Diffuse inflammatory infiltrates consisting of interstitial and peribronchial lymphocytes and interalveolar macrophages were reported (13,66,91). Another autopsy study showed that severely damaged lungs from patients who died early had low interferon-stimulated genes (ISGs), low viral loads and abundant infiltrating activated CD8 + T cells and macrophages (71).…”

Section: Immune Cells In Covid-19 Lungmentioning

confidence: 99%

Mechanisms of Lung Injury Induced by SARS-CoV-2 Infection

et al. 2022

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The lung is the major target organ of SARS-CoV-2 infection, which causes COVID-19. Here, we outline the multi-step mechanisms of lung epithelial and endothelial injury induced by SARS-CoV-2: direct viral infection, chemokine/cytokine-mediated damage, and immune cell-mediated lung injury. Finally, we discuss the recent progress in terms of anti-viral therapeutics as well as the development of anti-inflammatory or immunomodulatory therapeutic approaches. This review also provides a systematic overview of the models for studying SARS-CoV-2 infection, and discusses how an understanding of mechanisms of lung injury will help identify potential targets for future drug development to mitigate lung injury.

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Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures

Abstract: Highlights d SARS-CoV-2 and H1N1-induced ARDS show unique transcriptional signatures d Tissue remodeling pathways dominate the transcriptional profile of SARS-CoV-2 ARDS d SARS-CoV-2/H1N1 double infection resembles the lung antiviral response to H1N1

Cited by 45 publications

References 43 publications

Persistent Right Ventricle Dilatation in SARS-CoV-2–Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support

Persistent Right Ventricle Dilatation in SARS-CoV-2–Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures

Mechanisms of Lung Injury Induced by SARS-CoV-2 Infection

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