STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters

Robbert Boudewijns, Hendrik Jan Thibaut, Suzanne J F Kaptein, Rong Li, Valentijn Vergote, Laura Seldeslachts, Johan Van Weyenbergh, Carolien De Keyzer, Lindsey Bervoets, Sapna Sharma, Laurens Liesenborghs, Ji Ma, Sander Jansen, Dominique Van Looveren, Thomas Vercruysse, Xinyu Wang, Dirk Jochmans, Erik Martens, Kenny Roose, Dorien De VliegerBert Schepens, Tina Van Buyten, Sofie Jacobs, Yanan Liu, Joan Martí-Carreras, Bert Vanmechelen, Tony Wawina-Bokalanga, Leen Delang, Joana Rocha-Pereira, Lotte Coelmont, Winston Chiu, Pieter Leyssen, Elisabeth Heylen, Dominique Schols, Lanjiao Wang, Lila Close, Jelle Matthijnssens, Marc Van Ranst, Veerle Compernolle, Georg Schramm, Koen Van Laere, Xavier Saelens, Nico Callewaert, Ghislain Opdenakker, Piet Maes, Birgit Weynand, Christopher Cawthorne, Greetje Vande Velde, Zhongde Wang, Johan Neyts, Kai Dallmeier

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Emergence of SARS-CoV-2 causing COVID-19 has resulted in 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 Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Original languageEnglish
Article number5838
JournalNature Communications
Issue number1
Publication statusPublished - 2020


  • Animals
  • Betacoronavirus/pathogenicity
  • COVID-19
  • Coronavirus Infections/immunology
  • Cricetinae
  • Disease Models, Animal
  • Immunity, Innate
  • Interferon Type I/genetics
  • Lung/pathology
  • Mice
  • Pandemics
  • Pneumonia, Viral/immunology
  • SARS-CoV-2
  • STAT2 Transcription Factor/genetics
  • Signal Transduction
  • Virus Replication


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