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

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