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. Hartman(University of Pittsburgh), Sham Nambulli(University of Pittsburgh), Cynthia M. McMillen(University of Pittsburgh), Alexander G. White(University of Pittsburgh), Natasha L. Tilston‐Lunel(University of Pittsburgh), Joseph R. Albe(University of Pittsburgh), Emily L. Cottle(University of Pittsburgh), Matthew D. Dunn(University of Pittsburgh), L. James Frye(University of Pittsburgh), Theron Gilliland(University of Pittsburgh), Emily Olsen(University of Pittsburgh), Katherine J. O’Malley(University of Pittsburgh), Madeline M. Schwarz(University of Pittsburgh), Jaime Tomko(University of Pittsburgh), Reagan C. Walker(University of Pittsburgh), Mengying Xia(University of Pittsburgh), Matthew Hartman(Allegheny Health Network), Edwin Klein(University of Pittsburgh), Charles A. Scanga(University of Pittsburgh), JoAnne L. Flynn(University of Pittsburgh), William B. Klimstra(University of Pittsburgh), Anita K. McElroy(University of Pittsburgh), Douglas S. Reed(University of Pittsburgh), W. Paul Duprex(University of Pittsburgh)
PLoS Pathogens
September 18, 2020
Cited by 145Open Access
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Abstract

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.


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