SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

The recent emergence of B.1.1.529, the Omicron variant1,2 has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling data suggesting that B.1.1.529 spike can bind more avidly to murine ACE23,4, we observed less infection in 129, C57BL/6, BALB/c, and K18-hACE2 transgenic mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

1. These authors contributed equally: Peter J. Halfmann, Shun Iida, Kiyoko Iwatsuki-Horimoto, Tadashi Maemura, Maki Kiso

Affiliations

1. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA

   Peter J. Halfmann, Tadashi Maemura, Ryan Wright & Yoshihiro Kawaoka

2. Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan

   Shun Iida, Noriko Nakajima & Tadaki Suzuki

3. Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

   Kiyoko Iwatsuki-Horimoto, Maki Kiso, Michiko Ujie, Mutsumi Ito, Ryuta Uraki, Yuko Sakai-Tagawa, Hiroshi Ueki, Seiya Yamayoshi, Masaki Imai & Yoshihiro Kawaoka

4. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

   Suzanne M. Scheaffer, Tamarand L. Darling, Astha Joshi, Baoling Ying, James Brett Case, Zhenlu Chong, Bradley Whitener, Zhenlu Chong, Larissa B. Thackray, Adrianus C. M. Boon & Michael S. Diamond

5. Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA

   Samantha Loeber

6. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

   Gagandeep Singh, Prajakta Warang, Lauren A. Chang, Viviana Simon, H. Alshammary, A. A. Amoako, S. Aslam, C. Cognigni, M. Espinoza-Moraga, M. Laporte, I. Mena, A. Rooker, L. A. Sominsky, Adolfo García-Sastre & Michael Schotsaert

7. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

   Gagandeep Singh, Prajakta Warang, Lauren A. Chang, Adolfo García-Sastre & Michael Schotsaert

8. Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA

   Stephanie L. Foster, Katharine Floyd, Mit Patel, Venkata-Viswanadh Edara & Mehul S. Suthar

9. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

   Juan Moliva, Matthew Gagne, Amy R. Henry, Daniel C. Douek, Nancy J. Sullivan & Robert A. Seder

10. The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan

    Ryuta Uraki, Hiroshi Ueki, Seiya Yamayoshi, Masaki Imai & Yoshihiro Kawaoka

11. Department of Animal Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, USA

    Rong Li, Yanan Liu, Deanna

1. Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA

   Mehul S. Suthar

2. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

   Adolfo García-Sastre

3. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA

   Adrianus C. M. Boon & Michael S. Diamond

4. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA

   Adrianus C. M. Boon & Michael S. Diamond

5. The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA

   Michael S. Diamond

Consortia

Consortium Mount Sinai Pathogen Surveillance (PSP) study group

• B. Alburquerque
• , H. Alshammary
• , A. A. Amoako
• , S. Aslam
• , R. Banu
• , C. Cognigni
• , M. Espinoza-Moraga
• , K. Farrugia
• , A. van de Guchte
• , Z. Khalil
• , M. Laporte
• , I. Mena
• , A. E. Paniz-Mondolfi
• , J. Polanco
• , A. Rooker
•  & L. A. Sominsky