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Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 severity in the aged, young, and humanized ACE2 SARS-CoV-2 hamster models

  1. Author:
    Cong, Yu
    Lee, Ji Hyun
    Perry, Donna L
    Cooper, Kurt
    Wang, Hui
    Dixit, Saurabh
    Liu, David X
    Feuerstein, Irwin M
    Solomon,Jeffrey
    Bartos, Christopher
    Seidel, Jurgen
    Hammoud, Dima A
    Adams, Ricky
    Anthony, Scott M
    Liang, Janie
    Schuko, Nicolette
    Li, Rong
    Liu, Yanan
    Wang, Zhongde
    Tarbet, E Bart
    Hischak, Amanda M W
    Hart, Randy
    Isic, Nejra
    Burdette, Tracey
    Drawbaugh, David
    Huzella, Louis M
    Byrum, Russell
    Ragland, Danny
    St Claire, Marisa C
    Wada, Jiro
    Kurtz, Jonathan R
    Hensley, Lisa E
    Schmaljohn, Connie S
    Holbrook, Michael R
    Johnson, Reed F
  2. Author Address

    Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA., Radiology and Imaging Sciences, Clinical Center, National Institute of Health, Bethesda, MD, USA., , Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA., Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA., Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA., Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA. Electronic address: michael.holbrook@nih.gov., Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA; SARS-CoV-2 Virology Core Laboratory, Division of Intramural Research, National Institutes of Health, Bethesda, MD, USA. Electronic address: johnsonreed@niaid.nih.gov.,
    1. Year: 2023
    2. Date: Apr 15
    3. Epub Date: 2023 04 15
  1. Journal: Antiviral Research
    1. Pages: 105605
  2. Type of Article: Article
  3. Article Number: 105605
  1. Abstract:

    This study compared disease progression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in three different models of golden hamsters: aged (˜60 weeks old) wild-type (WT), young (6 weeks old) WT, and adult (14-22 weeks old) hamsters expressing the human-angiotensin-converting enzyme 2 (hACE2) receptor. After intranasal (IN) exposure to the SARS-CoV-2 Washington isolate (WA01/2020), 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography with computed tomography (18F-FDG PET/CT) was used to monitor disease progression in near real-time and animals were euthanized at pre-determined time points to directly compare imaging findings with other disease parameters associated with coronavirus disease 2019 (COVID-19). Consistent with histopathology, 18F-FDG-PET/CT demonstrated that aged WT hamsters exposed to 105 plaque forming units (PFU) developed more severe and protracted pneumonia than young WT hamsters exposed to the same (or lower) dose or hACE2 hamsters exposed to a uniformly lethal dose of virus. Specifically, aged WT hamsters presented with a severe interstitial pneumonia through 8 d post-exposure (PE), while pulmonary regeneration was observed in young WT hamsters at that time. hACE2 hamsters exposed to 100 or 10 PFU virus presented with a minimal to mild hemorrhagic pneumonia but succumbed to SARS-CoV-2-related meningoencephalitis by 6 d PE suggesting this model might allow assessment of SARS-CoV-2 infection on the central nervous system (CNS). Our group is the first to use (18F-FDG) PET/CT to differentiate respiratory disease severity ranging from mild to severe in three COVID hamster models. The non-invasive, serial measure of disease progression provided by PET/CT makes it a valuable tool for animal model characterization. Copyright © 2023. Published by Elsevier B.V.

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External Sources

  1. DOI: 10.1016/j.antiviral.2023.105605
  2. PMID: 37068595
  3. PMCID: PMC10105383
  4. PII : S0166-3542(23)00083-9

Library Notes

  1. Fiscal Year: FY2022-2023
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