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COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Chua, Robert Lorenz; Lukassen, Soeren; Trump, Saskia; Hennig, Bianca P; Wendisch, Daniel; Pott, Fabian; Debnath, Olivia; Thürmann, Loreen; Kurth, Florian; Völker, Maria Theresa; Kazmierski, Julia; Timmermann, Bernd; Twardziok, Sven; Schneider, Stefan; Machleidt, Felix; Müller-Redetzky, Holger; Maier, Melanie; Krannich, Alexander; Schmidt, Sein; Balzer, Felix; Liebig, Johannes; Loske, Jennifer; Suttorp, Norbert; Eils, Jürgen; Ishaque, Naveed; Liebert, Uwe Gerd; von Kalle, Christof; Hocke, Andreas; Witzenrath, Martin; Goffinet, Christine; Drosten, Christian; Laudi, Sven; Lehmann, Irina; Conrad, Christian; Sander, Leif-Erik; Eils, Roland.
Afiliación
  • Chua RL; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Lukassen S; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Trump S; Molecular Epidemiology Unit, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Hennig BP; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Wendisch D; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Pott F; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Debnath O; Berlin Institute of Health (BIH), Berlin, Germany.
  • Thürmann L; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Kurth F; Molecular Epidemiology Unit, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Völker MT; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Kazmierski J; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Timmermann B; Department of Anesthesiology and Intensive Care, University Hospital Leipzig, Leipzig, Germany.
  • Twardziok S; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Schneider S; Berlin Institute of Health (BIH), Berlin, Germany.
  • Machleidt F; Sequencing Core Facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Müller-Redetzky H; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Maier M; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Krannich A; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Schmidt S; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Balzer F; Institute of Virology, University Hospital Leipzig, Leipzig, Germany.
  • Liebig J; Clinical Study Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Loske J; Clinical Study Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Suttorp N; Department of Anestesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Eils J; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Ishaque N; Molecular Epidemiology Unit, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Liebert UG; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • von Kalle C; German Center for Lung Research (DZL), Berlin, Germany.
  • Hocke A; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Witzenrath M; Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Goffinet C; Institute of Virology, University Hospital Leipzig, Leipzig, Germany.
  • Drosten C; Clinical Study Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Laudi S; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Lehmann I; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Conrad C; German Center for Lung Research (DZL), Berlin, Germany.
  • Sander LE; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
  • Eils R; Berlin Institute of Health (BIH), Berlin, Germany.
Nat Biotechnol ; 38(8): 970-979, 2020 08.
Article en En | MEDLINE | ID: mdl-32591762
To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía Viral / Sistema Respiratorio / Infecciones por Coronavirus / Análisis de la Célula Individual / Transcriptoma Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía Viral / Sistema Respiratorio / Infecciones por Coronavirus / Análisis de la Célula Individual / Transcriptoma Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos