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 Erik Sander, Norbert Suttorp, Markus Ralser, Dieter Beule, Achim D. Gruber, Christine Goffinet, Markus Landthaler, Jakob Trimpert, Martin Witzenrath
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.