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Antiviral Res . Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 s

tetano

Editor, Senior Moderator
Antiviral Res


. 2023 Apr 15;105605.
doi: 10.1016/j.antiviral.2023.105605. Online ahead of print.
Longitudinal analyses using [SUP]18[/SUP]F-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


Yu Cong[SUP] 1 [/SUP], Ji Hyun Lee[SUP] 2 [/SUP], Donna L Perry[SUP] 1 [/SUP], Kurt Cooper[SUP] 1 [/SUP], Hui Wang[SUP] 1 [/SUP], Saurabh Dixit[SUP] 1 [/SUP], David X Liu[SUP] 1 [/SUP], Irwin M Feuerstein[SUP] 1 [/SUP], Jeffrey Solomon[SUP] 3 [/SUP], Christopher Bartos[SUP] 1 [/SUP], Jurgen Seidel[SUP] 1 [/SUP], Dima A Hammoud[SUP] 4 [/SUP], Ricky Adams[SUP] 1 [/SUP], Scott M Anthony[SUP] 1 [/SUP], Janie Liang[SUP] 1 [/SUP], Nicolette Schuko[SUP] 1 [/SUP], Rong Li[SUP] 5 [/SUP], Yanan Liu[SUP] 5 [/SUP], Zhongde Wang[SUP] 5 [/SUP], E Bart Tarbet[SUP] 5 [/SUP], Amanda M W Hischak[SUP] 1 [/SUP], Randy Hart[SUP] 1 [/SUP], Nejra Isic[SUP] 1 [/SUP], Tracey Burdette[SUP] 6 [/SUP], David Drawbaugh[SUP] 1 [/SUP], Louis M Huzella[SUP] 1 [/SUP], Russell Byrum[SUP] 1 [/SUP], Danny Ragland[SUP] 1 [/SUP], Marisa C St Claire[SUP] 1 [/SUP], Jiro Wada[SUP] 1 [/SUP], Jonathan R Kurtz[SUP] 1 [/SUP], Lisa E Hensley[SUP] 1 [/SUP], Connie S Schmaljohn[SUP] 1 [/SUP], Michael R Holbrook[SUP] 7 [/SUP], Reed F Johnson[SUP] 8 [/SUP]



Affiliations

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 ([SUP]18[/SUP]F-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, [SUP]18[/SUP]F-FDG-PET/CT demonstrated that aged WT hamsters exposed to 10[SUP]5[/SUP] 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 ([SUP]18[/SUP]F-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.

Keywords: 2-Deoxy-2-[fluorine-18]fluoro-D-glucose ((18)F-FDG) PET/CT; Animal models; COVID-19; Computed tomography (CT); Hamsters; SARS-CoV-2.
 
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