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

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

doi:10.1101/2020.12.18.423524

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bioRxiv · 10.1101/2020.12.18.423524

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

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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.

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Nouailles, G., Wyler, E., Pennitz, P., Postmus, D., Vladimirova, D., Kazmierski, J., Pott, F., Dietert, K., Mülleder, M., Farztdinov, V., Obermayer, B., Wienhold, S.-M., Andreotti, S., Höfler, T., Sawitzki, B., Drosten, C., Sander, L. E., Suttorp, N., Ralser, M., Beule, D., Gruber, A. D., Goffinet, C., Landthaler, M., Trimpert, J., Witzenrath, M.. 2020-12-19. Longitudinal omics in Syrian hamsters integrated with human data unravel complexity of moderate immune responses to SARS-CoV-2. https://doi.org/10.1101/2020.12.18.423524

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