SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and shedding of infectious virus from both respiratory and gastrointestinal tracts.
Amy L HartmanSham NambulliCynthia M McMillenAlexander G WhiteNatasha Louise Tilston-LunelJoseph R AlbeEmily CottleMatthew D DunnL James FryeTheron H GillilandEmily L OlsenKatherine J O'MalleyMadeline M SchwarzJaime A TomkoReagan C WalkerMengying XiaMatthew S HartmanEdwin KleinCharles A ScangaJoanne L FlynnWilliam B KlimstraAnita K McElroyDouglas S ReedW Paul DuprexPublished in: PLoS pathogens (2020)
Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an species to study mild/subclinical COVID-19 disease and with possible insights into live virus shedding. Future vaccine evaluation can be performed in AGM with correlates of efficacy being lung lesions by PET/CT, virus shedding, and tissue viral load.
Keyphrases
- positron emission tomography
- pet ct
- computed tomography
- sars cov
- coronavirus disease
- endothelial cells
- respiratory syndrome coronavirus
- pet imaging
- induced pluripotent stem cells
- magnetic resonance imaging
- high resolution
- gene expression
- blood glucose
- single cell
- blood brain barrier
- insulin resistance
- middle aged
- mass spectrometry
- fluorescence imaging