Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

Geraldine Nouailles (), Emanuel Wyler (), Peter Pennitz, Dylan Postmus, Daria Vladimirova, Julia Kazmierski, Fabian Pott, Kristina Dietert, Michael Muelleder, Vadim Farztdinov, Benedikt Obermayer, Sandra-Maria Wienhold, Sandro Andreotti, Thomas Hoefler, Birgit Sawitzki, Christian Drosten, Leif E. Sander, Norbert Suttorp, Markus Ralser, Dieter Beule, Achim D. Gruber, Christine Goffinet, Markus Landthaler, Jakob Trimpert () and Martin Witzenrath ()
Additional contact information
Geraldine Nouailles: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation
Emanuel Wyler: Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
Peter Pennitz: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation
Dylan Postmus: Berlin Institute of Health (BIH)
Daria Vladimirova: Freie Universität Berlin
Julia Kazmierski: Berlin Institute of Health (BIH)
Fabian Pott: Berlin Institute of Health (BIH)
Kristina Dietert: Freie Universität Berlin
Michael Muelleder: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Core Facility – High-Throughput Mass Spectrometry
Vadim Farztdinov: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Core Facility – High-Throughput Mass Spectrometry
Benedikt Obermayer: Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Core Unit Bioinformatics
Sandra-Maria Wienhold: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation
Sandro Andreotti: Freie Universität Berlin
Thomas Hoefler: Freie Universität Berlin
Birgit Sawitzki: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Immunology
Christian Drosten: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology
Leif E. Sander: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine
Norbert Suttorp: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine
Markus Ralser: The Francis Crick Institute, Molecular Biology of Metabolism Laboratory
Dieter Beule: Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Core Unit Bioinformatics
Achim D. Gruber: Freie Universität Berlin
Christine Goffinet: Berlin Institute of Health (BIH)
Markus Landthaler: Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
Jakob Trimpert: Freie Universität Berlin
Martin Witzenrath: Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.

Date: 2021
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DOI: 10.1038/s41467-021-25030-7

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