PT  - JOURNAL ARTICLE
AU  - Stefanie Deinhardt-Emmer
AU  - Sarah Böttcher
AU  - Clio Häring
AU  - Liane Giebeler
AU  - Andreas Henke
AU  - Roland Zell
AU  - Franziska Hornung
AU  - Christian Brandt
AU  - Mike Marquet
AU  - Alexander S. Mosig
AU  - Mathias W. Pletz
AU  - Michael Schacke
AU  - Jürgen Rödel
AU  - Regine Heller
AU  - Sandor Nietzsche
AU  - Bettina Löffler
AU  - Christina Ehrhardt
TI  - SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction
AID  - 10.1101/2020.08.31.276725
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.31.276725
4099  - http://biorxiv.org/content/early/2020/09/02/2020.08.31.276725.short
4100  - http://biorxiv.org/content/early/2020/09/02/2020.08.31.276725.full
AB  - Infections with SARS-CoV-2 lead to mild to severe coronavirus disease-19 (COVID-19) with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses.To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human alveolus-on-a-chip model composed of epithelial, endothelial, and mononuclear cells.Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including the interferon expression. By contrast, the adjacent endothelial layer was no infected and did neither show productive virus replication or interferon release. With prolonged infection, both cell types are damaged, and the barrier function is deteriorated, allowing the viral particles to overbear.In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokine release, which results in the damage of the alveolar barrier function and viral dissemination.