Severe acute respiratory disease in American mink experimentally infected with SARS-CoV-2

Danielle R. Adney,1,2 Jamie Lovaglio,3 Jonathan E. Schulz,1 Claude Kwe Yinda,1 Victoria A. Avanzato,1 Elaine Haddock,1 Julia R. Port,1 Myndi G. Holbrook,1 Patrick W. Hanley,2 Greg Saturday,3 Dana Scott,3 Carl Shaia,3 Andrew M. Nelson,2 Jessica R. Spengler,4 Cassandra Tansey,4 Caitlin M. Cossaboom,4 Natalie M. Wendling,4 Craig Martens,5 John Easley,6 Seng Wai Yap,7 Stephanie N. Seifert,8 and Vincent J. Munster1

1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

2Lovelace Biomedical Research Institute, Department of Comparative Medicine, Albuquerque, New Mexico, USA.

3Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

4Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

6Mink Veterinary Consulting and Research Service, Glenbeulah, Wisconsin, USA.

7Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

8Paul G. Allen School for Global Health, Washington State University, Pullman, Washington, USA.

Address correspondence to: Stephanie N. Seifert; 240 SE Ott Road, Allen Center, Pullman, Washington 99163, USA. Phone: 509.335.3831; Email: stephanie.seifert@wsu.edu. Or to: Vincent J. Munster; 903 S 4th Street, Hamilton, Montana 59840, USA. Phone: 406.375.7489; Email: vincent.munster@nih.gov.

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Published November 22, 2022 - More info

Published in Volume 7, Issue 22 on November 22, 2022
JCI Insight. 2022;7(22):e159573. https://doi.org/10.1172/jci.insight.159573.
© 2022 Adney et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Published November 22, 2022 - Version history
Received: February 22, 2022; Accepted: October 11, 2022 View PDF

An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, models that develop severe disease are still needed. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding nonstructural protein 6 in open reading frame 1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID-19 and, as such, are uniquely suited to test viral countermeasures.

Development of animal models has been a critical need since the emergence of SARS-CoV-2 to test vaccines and viral countermeasures (1). Multiple SARS-CoV-2 models of traditional laboratory species, including mice, hamsters, ferrets, and nonhuman primates, have been developed (2–6). However, many of these models either result in mild to moderate disease, experience distinctive viral dissemination due to altered angiotensin-converting enzyme 2 (ACE2) expression, specifically in the brain, or fail to develop clinical acute respiratory disease syndrome (ARDS) (2, 3, 6). SARS-CoV-2 in experimentally infected mink is known to cause pathogenesis reminiscent of severe COVID-19 in humans (7); however, additional characterization of this model is still needed. This model could allow experimental research into the pathogenesis of severe COVID-19 and would facilitate the evaluation of therapeutic countermeasures in the context of severe disease.

Experimental infections of ferrets resulted in viral replication and transmission to naive individuals but very minimal to mild clinical signs of disease (4, 5). However, this does not appear to be the case for all members of the Mustelidae family (4, 5, 8–10). Reports of farmed mink (Neogale vison) infected with SARS-CoV-2 emerged in the Netherlands in April 2020 (11). To date, at least 12 countries have reported outbreaks in farmed mink, and there have been 2 reports describing positive feral or escaped mink (12, 13). While many naturally infected mink exhibited mild to moderate clinical disease, a subset of these animals experienced an acute interstitial pneumonia that manifested with severe respiratory distress (11, 14). Genomic surveillance in samples originating from mink in Denmark identified a series of changes in SARS-CoV-2 spike protein, known as the Cluster 5 variant (15). This mink-associated variant resulted in reduced neutralization with human convalescent sera in vitro (15). A high susceptibility to infection coupled with the public health risk of intrahost viral evolution prompted massive culls of an estimated 17 million mink on Danish farms (16).

Here, we show that experimentally infected mink develop a severe acute respiratory infection. After infection, progressive respiratory disease can be observed clinically, radiographically, and by histopathology. High amounts of viral RNA and infectious virus can be detected from the respiratory tract. Deep sequencing of SARS-CoV-2 genomes from oral swabs and lung tissue samples collected 3 days post inoculation (dpi) demonstrate rapid enrichment for a nonsynonymous mutation in the gene encoding for the nonstructural protein 6 (nsp6) in ORF1a in lung tissue samples. These data indicate the potential for rapid viral evolution in mink at the human-animal interface in a short time frame. Together, these data suggest that the mink animal model recapitulates severe disease observed in hospitalized and fatal human cases of COVID-19 and could be useful to test countermeasures against severe COVID-19.

Mink ACE2 supports efficient entry of SARS-CoV-2. To evaluate the utility of the mink model for COVID-19, we compared human and mink ACE2 functional receptor entry using structural analysis and a vesicular stomatitis virus pseudotype entry assay (17). The sequence of mink ACE2 was obtained by sequencing from lung tissue. The obtained mink ACE2 sequence is 99.8% identical to the previously published Neogale vison ACE2 sequence (GenBank QPL1221.1). Two substituti

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