PT  - JOURNAL ARTICLE
AU  - Robbert Boudewijns
AU  - Hendrik Jan Thibaut
AU  - Suzanne J. F. Kaptein
AU  - Rong Li
AU  - Valentijn Vergote
AU  - Laura Seldeslachts
AU  - Carolien De Keyzer
AU  - Sapna Sharma
AU  - Sander Jansen
AU  - Johan Van Weyenbergh
AU  - Ji Ma
AU  - Erik Martens
AU  - Lindsey Bervoets
AU  - Tina Van Buyten
AU  - Sofie Jacobs
AU  - Yanan Liu
AU  - Joan Martí-Carreras
AU  - Bert Vanmechelen
AU  - Tony Wawina-Bokalanga
AU  - Leen Delang
AU  - Joana Rocha-Pereira
AU  - Lotte Coelmont
AU  - Winston Chiu
AU  - Pieter Leyssen
AU  - Elisabeth Heylen
AU  - Dominique Schols
AU  - Lanjiao Wang
AU  - Lila Close
AU  - Jelle Matthijnssens
AU  - Marc Van Ranst
AU  - Georg Schramm
AU  - Koen Van Laere
AU  - Ghislain Opdenakker
AU  - Piet Maes
AU  - Birgit Weynand
AU  - Christopher Cawthorne
AU  - Greetje Vande Velde
AU  - Zhongde Wang
AU  - Johan Neyts
AU  - Kai Dallmeier
TI  - STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters
AID  - 10.1101/2020.04.23.056838
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.23.056838
4099  - http://biorxiv.org/content/early/2020/04/23/2020.04.23.056838.short
4100  - http://biorxiv.org/content/early/2020/04/23/2020.04.23.056838.full
AB  - Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and prospected hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS-CoV-2. In wild-type hamsters, SARS-CoV-2 infection triggers bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. We further assess SARS-CoV-2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Finally, we identify an exuberant innate response as key player in immune pathogenesis, in which STAT2 signaling plays a double-edged role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results endorse hamsters as pre-clinical model to rationalize and assess the therapeutic benefit of new antivirals or immune modulators for the treatment of COVID-19 patients.Competing Interest StatementThe authors have declared no competing interest.