Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19.
journal contributionposted on 2021-08-17, 08:46 authored by 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 Witzenrath
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.