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Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis)

View ORCID ProfileCourtney L. Finch, View ORCID ProfileIan Crozier, Ji Hyun Lee, Russ Byrum, Timothy K. Cooper, Janie Liang, Kaleb Sharer, Jeffrey Solomon, View ORCID ProfilePhilip J. Sayre, Gregory Kocher, Christopher Bartos, Nina M. Aiosa, View ORCID ProfileMarcelo Castro, Peter A. Larson, View ORCID ProfileRicky Adams, View ORCID ProfileBrett Beitzel, Nicholas Di Paola, Jeffrey R. Kugelman, Jonathan R. Kurtz, Tracey Burdette, Martha C. Nason, Irwin M. Feuerstein, View ORCID ProfileGustavo Palacios, View ORCID ProfileMarisa C. St. Claire, View ORCID ProfileMatthew G. Lackemeyer, View ORCID ProfileReed F. Johnson, View ORCID ProfileKatarina M. Braun, Mitchell D. Ramuta, View ORCID ProfileJiro Wada, View ORCID ProfileConnie S. Schmaljohn, View ORCID ProfileThomas C. Friedrich, View ORCID ProfileDavid H. O’Connor, View ORCID ProfileJens H. Kuhn
doi: https://doi.org/10.1101/2020.05.14.096727
Courtney L. Finch
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Ian Crozier
2Integrated Research Facility at Fort Detrick, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research supported by the National Cancer Institute, Frederick, MD 21702, USA
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Ji Hyun Lee
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Russ Byrum
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Timothy K. Cooper
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Janie Liang
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Kaleb Sharer
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Jeffrey Solomon
2Integrated Research Facility at Fort Detrick, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research supported by the National Cancer Institute, Frederick, MD 21702, USA
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Philip J. Sayre
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Gregory Kocher
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Christopher Bartos
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Nina M. Aiosa
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
3Center for Infectious Disease Imaging, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, 20814, USA
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Marcelo Castro
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Peter A. Larson
4United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA
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Ricky Adams
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Brett Beitzel
4United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA
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Nicholas Di Paola
4United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA
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Jeffrey R. Kugelman
4United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA
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Jonathan R. Kurtz
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Tracey Burdette
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Martha C. Nason
5Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
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Irwin M. Feuerstein
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Gustavo Palacios
4United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA
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Marisa C. St. Claire
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Matthew G. Lackemeyer
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Reed F. Johnson
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Katarina M. Braun
6Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
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Mitchell D. Ramuta
7Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA
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Jiro Wada
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Connie S. Schmaljohn
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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Thomas C. Friedrich
6Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
8Wisconsin National Primate Research Center, Madison, WI 53706, USA
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  • For correspondence: tfriedri@wisc.edu dhoconno@wisc.edu kuhnjens@mail.nih.gov
David H. O’Connor
7Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA
8Wisconsin National Primate Research Center, Madison, WI 53706, USA
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  • For correspondence: tfriedri@wisc.edu dhoconno@wisc.edu kuhnjens@mail.nih.gov
Jens H. Kuhn
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
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  • For correspondence: tfriedri@wisc.edu dhoconno@wisc.edu kuhnjens@mail.nih.gov
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an exponentially increasing number of coronavirus disease 19 (COVID-19) cases globally. Prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of COVID-19 animal models that enable accurate, quantifiable, and reproducible measurement of COVID-19 pulmonary disease free from observer bias. We first used serial computed tomography (CT) to demonstrate that bilateral intrabronchial instillation of SARS-CoV-2 into crab-eating macaques (Macaca fascicularis) results in mild-to-moderate lung abnormalities qualitatively characteristic of subclinical or mild-to-moderate COVID-19 (e.g., ground-glass opacities with or without reticulation, paving, or alveolar consolidation, peri-bronchial thickening, linear opacities) at typical locations (peripheral>central, posterior and dependent, bilateral, multi-lobar). We then used positron emission tomography (PET) analysis to demonstrate increased FDG uptake in the CT-defined lung abnormalities and regional lymph nodes. PET/CT imaging findings appeared in all macaques as early as 2 days post-exposure, variably progressed, and subsequently resolved by 6–12 days post-exposure. Finally, we applied operator-independent, semi-automatic quantification of the volume and radiodensity of CT abnormalities as a possible primary endpoint for immediate and objective efficacy testing of candidate medical countermeasures.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/artic-network/artic-ncov2019/tree/master/primer_schemes/nCoV-2019/V1

  • https://openresearch.labkey.com/project/Coven/COVID-001/begin.view

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis)
Courtney L. Finch, Ian Crozier, Ji Hyun Lee, Russ Byrum, Timothy K. Cooper, Janie Liang, Kaleb Sharer, Jeffrey Solomon, Philip J. Sayre, Gregory Kocher, Christopher Bartos, Nina M. Aiosa, Marcelo Castro, Peter A. Larson, Ricky Adams, Brett Beitzel, Nicholas Di Paola, Jeffrey R. Kugelman, Jonathan R. Kurtz, Tracey Burdette, Martha C. Nason, Irwin M. Feuerstein, Gustavo Palacios, Marisa C. St. Claire, Matthew G. Lackemeyer, Reed F. Johnson, Katarina M. Braun, Mitchell D. Ramuta, Jiro Wada, Connie S. Schmaljohn, Thomas C. Friedrich, David H. O’Connor, Jens H. Kuhn
bioRxiv 2020.05.14.096727; doi: https://doi.org/10.1101/2020.05.14.096727
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Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis)
Courtney L. Finch, Ian Crozier, Ji Hyun Lee, Russ Byrum, Timothy K. Cooper, Janie Liang, Kaleb Sharer, Jeffrey Solomon, Philip J. Sayre, Gregory Kocher, Christopher Bartos, Nina M. Aiosa, Marcelo Castro, Peter A. Larson, Ricky Adams, Brett Beitzel, Nicholas Di Paola, Jeffrey R. Kugelman, Jonathan R. Kurtz, Tracey Burdette, Martha C. Nason, Irwin M. Feuerstein, Gustavo Palacios, Marisa C. St. Claire, Matthew G. Lackemeyer, Reed F. Johnson, Katarina M. Braun, Mitchell D. Ramuta, Jiro Wada, Connie S. Schmaljohn, Thomas C. Friedrich, David H. O’Connor, Jens H. Kuhn
bioRxiv 2020.05.14.096727; doi: https://doi.org/10.1101/2020.05.14.096727

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