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

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 spat...

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Published in:bioRxiv 2020-12
Main Authors: Nouailles, Geraldine, Wyler, Emanuel, Pennitz, Peter, Postmus, Dylan, Vladimirova, Daria, Kazmierski, Julia, Pott, Fabian, Dietert, Kristina, Mülleder, Michael, Farztdinov, Vadim, Obermayer, Benedikt, Sandra-Maria Wienhold, Andreotti, Sandro, Höfler, Thomas, Sawitzki, Birgit, Drosten, Christian, Sander, Leif Erik, Suttorp, Norbert, Ralser, Markus, Beule, Dieter, Gruber, Achim Dieter, Goffinet, Christine, Landthaler, Markus, Trimpert, Jakob, Witzenrath, Martin
Format: Article
Language:English
Subjects:
CD4 antigen
CD8 antigen
Coronaviruses
COVID-19
Cytotoxicity
Endothelial cells
Epithelial cells
Host-pathogen interactions
Immune response
Inflammation
Lymphocytes T
Macrophages
Monocytes
Proteomics
Research funding
Severe acute respiratory syndrome coronavirus 2
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Summary: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. Competing Interest Statement G.N. received funding for research from Biotest AG. E.W. P.P, D.P.,D.V.,J.K., F.P., K.D., M.M., V.F., B.O., S.-M.W, S.A., T.H., B.S., C.D., L.E.S., N.S., M.R., D.B., A.D.G., C.G., M.L., J.T declare no conflict of interest. M.W. received funding for research from Actelion, Bayer Health Care, Biotest AG, Boehringer Ingelheim, Noxxon, Pantherna, Quark Pharma, Vaxxilon, and for advisory from Actelion, Aptarion, Astra Zeneca, Bayer Health Care, Berlin Chemie, Biotest, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Novartis, Noxxon, Pantherna, Teva and Vaxxilon. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. Footnotes * https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162208 * https://github.com/Berlin-Hamster-Single-Cell-Consortium
DOI:10.1101/2020.12.18.423524