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

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 clinicalgrade 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-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.

Susceptibility of rabbits to SARS-CoV-2

“…This pattern is potentially linked to early innate immune responses that act within days, followed by adaptive responses that generally take one week to be activated. These observations are in line with recent findings that the presence of neutralizing serum antibodies in humans negatively correlates with infectious virus shedding, and that shedding of viral RNA outlasts shedding of infectious virus [ 17 ]. The presence of eosinophils in the nose and lungs of infected animals suggests a possible helper T cell 2 (Th2)-mediated immune response.…”

Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

“…Intrinsic species-specific susceptibility to disease progression has been described for NHP in SARS-CoV-1 6 with AGM being more susceptible than rhesus to severe disease. There were unexpected similarities in the kinetics and the quality of the immune responses analyzed in RM and AGM, particularly during the acute phase of infection, however, AGM did not clear the infection, as well as RM and two AGM, had the most severe symptoms 56 . While the number of animals enrolled in this study was not sufficient to look at species-specific differences and their effect on disease progression, we found that a higher ratio of IL-10: IL-6 in plasma was associated with disease severity.…”

Therapeutic MK-4482/EIDD-2801 Blocks SARS-CoV-2 Transmission in Ferrets

“…Representatives of a number of animal species such as non-human primates 19 , dogs 20 , cats 20 , ferrets 20 , hamsters [21][22][23] , and bats 16 were susceptible to SARS-CoV-2 without prior species adaptation when infected experimentally. Natural infection has been documented for felines 24…”