Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. 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 6. 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.

Fatai S. Oladunni, Jun-Gyu Park, Paula A. Pino, Olga Gonzalez, Anwari Akhter, Anna Allué-Guardia, Angélica Olmo-Fontánez, Shalini Gautam, Andreu Garcia-Vilanova, Chengjin Ye, Kevin Chiem, Colwyn Headley, Varun Dwivedi, Laura M. Parodi, Kendra J. Alfson, Hilary M. Staples, Alyssa Schami, Juan I. Garcia, Alison Whigham, Roy Neal Platt II, Michal Gazi, Jesse Martinez, Colin Chuba, Stephanie Earley, Oscar H. Rodriguez, Stephanie Davis Mdaki, Katrina N. Kavelish, Renee Escalona, Cory R. A. Hallam, Corbett Christie, Jean L. Patterson, Tim J. C. Anderson, Ricardo Carrion Jr, Edward J. Dick Jr, Shannan Hall-Ursone, Larry S. Schlesinger, Xavier Alvarez, Deepak Kaushal, Luis D. Giavedoni, Joanne Turner, Luis Martinez-Sobrido, Jordi B. Torrelles