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    Single-cell-sequencing in SARS-COV-2-infected hamsters sheds light on endothelial cell involvement in COVID-19 (2021)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Nouailles, Geraldine
    Wyler, Emanuel
    Pennitz, Peter
    Postmus, Dylan
    Vladimirova, Daria (WE 5)
    Kazmierski, Julia
    Pott, Fabian
    Dietert, Kristina (Tiermedizinisches Zentrum für Resistenzforschung)
    Muelleder, Michael
    Farztdinov, Vadim
    Obermayer, Benedikt
    Wienhold, Sandra-Maria
    Andreotti, Sandro
    Hoefler, Thomas (WE 5)
    Sawitzki, Birgit
    Drosten, Christian
    Sander, Leif E.
    Suttorp, Norbert
    Ralser, Markus
    Beule, Dieter
    Gruber, Achim Dieter (WE 12)
    Goffinet, Christine
    Landthaler, Markus
    Trimpert, Jakob (WE 5)
    Witzenrath, Martin
    Quelle
    The European respiratory journal
    Bandzählung: 58
    Heftzählung: Suppl.1 : ERS International Congress 2021 abstracts
    Seiten: Abstract PA2355
    ISSN: 0903-1936
    Sprache
    Englisch
    Verweise
    URL (Volltext): http://erj.ersjournals.com/lookup/doi/10.1183/13993003.congress-2021.PA2355
    DOI: 10.1183/13993003.congress-2021.PA2355
    Kontakt
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    14163 Berlin
    +49 30 838 51833
    virologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Background:
    Pulmonary and systemic immune responses influence disease severity in COVID-19, and could be key to therapeutic strategies.

    Aims and objectives:
    To investigate cellular mechanisms contributing to defense or fostering detrimental inflammatory lung injury, focusing on the clinically ill-defined involvement of endothelial cells.

    Methods:
    Using SARS-CoV-2-infected Syrian and Roborovski hamsters as models for moderate and severe COVID-19, respectively, a detailed and longitudinal analysis of systemic and pulmonary quantitative and qualitative immune responses was conducted. Hamster omics were corroborated with datasets from COVID-19 patients.

    Results:
    By integrating data from COVID-19 patients, inter-species concordance of cellular and molecular host-pathogen interactions was demonstrated. In moderate disease the earliest and strongest transcriptional response following SARS-CoV-2 infection, including pro-inflammatory genes, was exerted by monocyte-derived macrophages in lungs, while epithelial cells showed only weak gene expression program changes. Notably, endothelial cells showed no evidence for infection but reacted by strong and early expression of anti-viral as well as pro-inflammatory and T cell recruiting genes, with variations depending on cell subtypes.

    Conclusions:
    Analysis of Syrian hamsters infected with SARS-CoV-2 identified cell type-specific effector functions, providing detailed insights into mechanisms of COVID-19, thus informing therapeutic strategies. Extended investigations in highly susceptible Roborosvki dwarf hamsters will complement our picture of moderate and severe disease courses.