Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19
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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 Martin WitzenrathAbstract
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.
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Journal Nature Communications
Volume 12
Issue number 1
Pages 4869
Available online
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Publisher website (DOI) 10.1038/s41467-021-25030-7
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Europe PubMed Central 34381043
Pubmed 34381043
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