PT  - JOURNAL ARTICLE
AU  - Kiener, Mirjam
AU  - De Maddalena, Lea
AU  - Roldan, Nuria
AU  - Thalmann, George N.
AU  - Geiser, Thomas
AU  - Hobi, Nina
AU  - Kruithof-De Julio, Marianna
TI  - Late Breaking Abstract - Organoids and lung-on-chip to study SARS-CoV-2-mediated lung injury
AID  - 10.1183/13993003.congress-2020.4149
DP  - 2020 Sep 07
TA  - European Respiratory Journal
PG  - 4149
VI  - 56
IP  - suppl 64
4099  - http://erj.ersjournals.com/content/56/suppl_64/4149.short
4100  - http://erj.ersjournals.com/content/56/suppl_64/4149.full
SO  - Eur Respir J2020 Sep 07; 56
AB  - COVID-19 is an infectious disease caused by the newly discovered coronavirus named SARS-CoV-2. The virus enters the body through the airways by exploiting the angiotensin-converting enzyme 2 (ACE2) and serine proteinase TMPRSS2. Thus, especially lung epithelial cells are attacked by the virus. In the distal lung, the virus infection leads to life-threatening alveolar damage and cytokine storm. Many excellent clinical studies described the pathology of COVID-19 progression in patients. However, impactful in vitro studies are still missing due to the exceptional difficulty to model the alveolar setting in vitro. Here, we introduce two advanced models based on organoids and lung-on-chip (LOC) technology. The models derived from primary alveolar epithelial cells were characterized by fluorescence imaging and gene expression. Barrier function and cell polarity were assessed by confocal microscopy of tight junction and transporter proteins. We showed that the LOC model and the newly developed organoids preserve alveolar type II specific markers (SP-C and HTII-280). In both models we could detect relevant amounts of ACE2 and TMPRSS2 mRNA as compared to whole lung extracts.As a next step we will optimize the infection titer for both systems to further analyze transcriptomic changes upon SARS-CoV-2 infection. The here presented advanced in vitro models, recapitulating the distal lung, serve as complementary SARS-CoV-2 lung infection models. The LOC model will allow to simulate alveolar breakdown and cytokine storm whereas the organoid models will facilitate high-content drug screening.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4149.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.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).