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Longitudinal omics in Syrian hamsters integrated with human data unravel complexity of moderate immune responses to SARS-CoV-2

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Item Type:Preprint
Title:Longitudinal omics in Syrian hamsters integrated with human data unravel complexity of moderate immune responses to SARS-CoV-2
Creators Name:Nouailles, G. and Wyler, E. and Pennitz, P. and Postmus, D. and Vladimirova, D. and Kazmierski, J. and Pott, F. and Dietert, K. and Mülleder, M. and Farztdinov, V. and Obermayer, B. and Wienhold, S.M. and Andreotti, S. and Höfler, T. and Sawitzki, B. and Drosten, C. and Sander, L.E. and Suttorp, N. and Ralser, M. and Beule, D. and Gruber, A.D. and Goffinet, C. and Landthaler, M. and Trimpert, J. and Witzenrath, M.
Abstract:In COVID-19, the immune response largely determines disease severity and is key to therapeutic strategies. Cellular mechanisms contributing to inflammatory lung injury and tissue repair in SARS-CoV-2 infection, particularly endothelial cell involvement, remain ill-defined. We performed detailed spatiotemporal analyses of cellular and molecular processes in SARS-CoV-2 infected Syrian hamsters. Comparison of hamster single-cell sequencing and proteomics with data sets from COVID-19 patients demonstrated inter-species concordance of cellular and molecular host-pathogen interactions. In depth vascular and pulmonary compartment analyses (i) supported the hypothesis that monocyte-derived macrophages dominate inflammation, (ii) revealed endothelial inflammation status and T-cell attraction, and (iii) showed that CD4+ and CD8+ cytotoxic T-cell responses precede viral elimination. Using the Syrian hamster model of self-limited moderate COVID-19, we defined the specific roles of endothelial and epithelial cells, among other myeloid and non-myeloid lung cell subtypes, for determining the disease course.
Keywords:Coronavirus Disease 2019, COVID-19, Syrian Hamster, SARS-CoV-2, Inflammatory Monocytes, Macrophages, Cytotoxic T Cells, Endothelial Cells, Animals, Mesocricetus auratus
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.12.18.423524
Date:19 December 2020
Official Publication:https://doi.org/10.1101/2020.12.18.423524

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