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

• DOI: 10.1371/journal.ppat.1008903
• Publication Date: 2020-09-18T17:45:27Z
• Authors: Amy L. Hartman; Sham Nambulli; Cynthia M. McMillen; Alexander G. White; Natasha Louise Ti...; Joseph R. Albe; Emily Cottle; Matthew D. Dunn; L. James Frye; Theron H. Gilliland; Emily L. Olsen; Katherine J. O’Ma...; Madeline M. Schwarz; Jaime A. Tomko; Reagan C. Walker; Mengying Xia; Matthew S. Hartman; Edwin Klein; Charles A. Scanga; JoAnne L. Flynn; William B. Klimstra; Anita K. McElroy; Douglas S. Reed; W. Paul Duprex
• Keywords: 0301 basic medicine; 0303 health sciences; QH301-705.5; SARS-CoV-2; Pneumonia, Viral; COVID-19; RC581-607; Virus Shedding; 3. Good health; Gastrointestinal Tract; Betacoronavirus; 03 medical and health sciences; Positron Emission Tomography Computed Tomography; Chlorocebus aethiops; Animals; Immunologic diseases. Allergy; Biology (General); Coronavirus Infections; Lung; Pandemics; Research Article

AbstractVaccines 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-grade18F-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.One Sentence SummarySubclinical infection of African green monkeys infected with SARS-CoV-2 results in prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts.