TY - JOUR T1 - Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice JF - bioRxiv DO - 10.1101/2020.07.18.210179 SP - 2020.07.18.210179 AU - Fatai S. Oladunni AU - Jun-Gyu Park AU - Paula Pino Tamayo AU - Olga Gonzalez AU - Anwari Akhter AU - Anna Allué-Guardia AU - Angélica Olmo-Fontánez AU - Shalini Gautam AU - Andreu Garcia-Vilanova AU - Chengjin Ye AU - Kevin Chiem AU - Colwyn Headley AU - Varun Dwivedi AU - Laura M. Parodi AU - Kendra J. Alfson AU - Hilary M. Staples AU - Alyssa Schami AU - Juan I. Garcia AU - Alison Whigham AU - Roy Neal Platt II AU - Michal Gazi AU - Jesse Martinez AU - Colin Chuba AU - Stephanie Earley AU - Oscar H Rodriguez AU - Stephanie Davis Mdaki AU - Katrina N Kavelish AU - Renee Escalona AU - Cory R. A. Hallam AU - Corbett Christie AU - Jean L. Patterson AU - Tim J. C. Anderson AU - Ricardo Carrion, Jr AU - Edward J. Dick, Jr AU - Shannan Hall-Ursone AU - Larry S. Schlesinger AU - Deepak Kaushal AU - Luis D. Giavedoni AU - Xavier Alvarez AU - Joanne Turner AU - Luis Martinez-Sobrido AU - Jordi B. Torrelles Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/19/2020.07.18.210179.abstract N2 - Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease currently lacks a validated small animal model. Here, we show that transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2-transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2-transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 4. K18 hACE2-transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.Competing Interest StatementThe authors have declared no competing interest. ER -