SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts

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...

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Published in:bioRxiv 2020-06
Main Authors: Hartman, Amy L, Nambulli, Shamkumar, Mcmillen, Cynthia M, White, Alexander G, Tilston-Lunel, Natasha, Albe, Joseph R, Cottle, Emily L, Dunn, Matthew D, Frye, Lonnie James, Gilliland, Theron H, Olsen, Emily L, O'malley, Katherine J, Schwarz, Madeline M, Tomko, Jaime A, Walker, Reagan C, Xia, Mengying, Hartman, Matthew S, Klein, Edwin, Scanga, Charles, Flynn, Joanne L, Klimstra, William B, Mcelroy, Anita K, Reed, Douglas S, Duprex, W Paul
Format: Article
Language:English
Subjects:
Aerosols
Computed tomography
Coronaviruses
COVID-19
Gastrointestinal tract
Glucose
Immunoglobulin G
Immunoglobulin M
Infections
Mucosa
Necropsy
Pandemics
Positron emission tomography
Pulmonary lesions
Respiratory diseases
Ribonucleic acid
RNA
Severe acute respiratory syndrome coronavirus 2
Therapeutic applications
Vaccines
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Summary: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 excellent species to study mild/subclinical COVID-19 disease and have shed light on unknown aspects of long-term virus shedding. They are ideally suited for preclinical evaluation of candidate vaccines and therapeutic interventions. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.06.20.137687