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

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Item Type:Article
Title:Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19
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 Muelleder, M. 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.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, 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.
Keywords:Alveolar Epithelial Cells, Animal Disease Models, COVID-19, Cytokines, Cytotoxic T-Lymphocytes, Endothelial Cells, Immunoglobulin M, Inflammation, Lung, Macrophages, Monocytes, SARS-CoV-2, Signal Transduction, Toll-Like Receptors, Animals, Cricetinae, Mesocricetus
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:12
Number:1
Page Range:4869
Date:11 August 2021
Official Publication:https://doi.org/10.1038/s41467-021-25030-7
PubMed:View item in PubMed

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