Longitudinal omics in Syrian hamsters integrated with human data unravel cellular effector responses to moderate COVID-19

Nouailles, Geraldine; Wyler, E.; Pennitz, P.; Postmus, D.; Vladrimirova, D.; Kazmierski, J.; Pott, F.; Dietert, K.; Mülleder, M.l; Farztdinov, V.; Obermayer, B.; Wienhold, S.M.; Andreotti, S.; Hoefler, T.; Sawitzki, B.; Drosten, C.; Sander, L.; Suttorp, N.; Ralser, M.; Beule, D.; Gruber, A.; Goffinet, C.; Landthaler, M.; Trimpert, J.; Witzenrath, M.

Longitudinal omics in Syrian hamsters integrated with human data unravel cellular effector responses to moderate COVID-19

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Item Type:	Preprint
Title:	Longitudinal omics in Syrian hamsters integrated with human data unravel cellular effector responses to moderate COVID-19
Creators Name:	Nouailles, Geraldine, Wyler, E., Pennitz, P., Postmus, D., Vladrimirova, D., Kazmierski, J., Pott, F., Dietert, K., Mülleder, M.l, Farztdinov, V., Obermayer, B., Wienhold, S.M., Andreotti, S., Hoefler, T., Sawitzki, B., Drosten, C., Sander, L., Suttorp, N., Ralser, M., Beule, D., Gruber, A., Goffinet, C., Landthaler, M., Trimpert, J. and Witzenrath, M.
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 model for moderate COVID-19, we conducted a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborated it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exerted the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells showed weak activation. Without evidence for productive infection, endothelial cells reacted, 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 preceded viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters can thus identify cell type-specific effector functions, provide detailed insights into pathomechanisms of COVID-19, and inform therapeutic strategies.
Keywords:	COVID-19, Immune Response, Disease Severity, Animals, Hamsters
Source:	Research Square
Title of Book:	Longitudinal omics in Syrian hamsters integrated with human data unravel cellular effector responses to moderate COVID-19
Publisher:	Research Square
Article Number:	rs-148392/v1
Date:	28 January 2021
Official Publication:	https://doi.org/10.21203/rs.3.rs-148392/v1

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