PT  - JOURNAL ARTICLE
AU  - Geraldine Nouailles
AU  - Emanuel Wyler
AU  - Peter Pennitz
AU  - Dylan Postmus
AU  - Daria Vladimirova
AU  - Julia Kazmierski
AU  - Fabian Pott
AU  - Kristina Dietert
AU  - Michael Muelleder
AU  - Vadim Farztdinov
AU  - Benedikt Obermayer
AU  - Sandra-Maria Wienhold
AU  - Sandro Andreotti
AU  - Thomas Hoefler
AU  - Birgit Sawitzki
AU  - Christian Drosten
AU  - Leif E. Sander
AU  - Norbert Suttorp
AU  - Markus Ralser
AU  - Dieter Beule
AU  - Achim D. Gruber
AU  - Christine Goffinet
AU  - Markus Landthaler
AU  - Jakob Trimpert
AU  - Martin Witzenrath
TI  - Single-cell-sequencing in SARS-COV-2-infected hamsters sheds light on endothelial cell involvement in COVID-19
AID  - 10.1183/13993003.congress-2021.PA2355
DP  - 2021 Sep 05
TA  - European Respiratory Journal
PG  - PA2355
VI  - 58
IP  - suppl 65
4099  - http://erj.ersjournals.com/content/58/suppl_65/PA2355.short
4100  - http://erj.ersjournals.com/content/58/suppl_65/PA2355.full
SO  - Eur Respir J2021 Sep 05; 58
AB  - Background: Pulmonary and systemic immune responses influence disease severity in COVID-19, and could be key to therapeutic strategies.Aims and objectives: To investigate cellular mechanisms contributing to defense or fostering detrimental inflammatory lung injury, focusing on the clinically ill-defined involvement of endothelial cells.Methods: Using SARS-CoV-2-infected Syrian and Roborovski hamsters as models for moderate and severe COVID-19, respectively, a detailed and longitudinal analysis of systemic and pulmonary quantitative and qualitative immune responses was conducted. Hamster omics were corroborated with datasets from COVID-19 patients.Results: By integrating data from COVID-19 patients, inter-species concordance of cellular and molecular host-pathogen interactions was demonstrated. In moderate disease the earliest and strongest transcriptional response following SARS-CoV-2 infection, including pro-inflammatory genes, was exerted by monocyte-derived macrophages in lungs, while epithelial cells showed only weak gene expression program changes. Notably, endothelial cells showed no evidence for infection but reacted by strong and early expression of anti-viral as well as pro-inflammatory and T cell recruiting genes, with variations depending on cell subtypes.Conclusions: Analysis of Syrian hamsters infected with SARS-CoV-2 identified cell type-specific effector functions, providing detailed insights into mechanisms of COVID-19, thus informing therapeutic strategies. Extended investigations in highly susceptible Roborosvki dwarf hamsters will complement our picture of moderate and severe disease courses.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2355.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).