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

Nouailles, Geraldine; Wyler, Emanuel; Pennitz, Peter; Postmus, Dylan; Vladimirova, Daria; Kazmierski, Julia; Pott, Fabian; Dietert, Kristina; Muelleder, Michael; Farztdinov, Vadim; Obermayer, Benedikt; Wienhold, Sandra-Maria; Andreotti, Sandro; Hoefler, Thomas; Sawitzki, Birgit; Drosten, Christian; Sander, Leif E.; Suttorp, Norbert; Ralser, Markus; Beule, Dieter; Gruber, Achim D.; Goffinet, Christine; Landthaler, Markus; Trimpert, Jakob; Witzenrath, Martin

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.