Pathogenesis and transmission of SARS-CoV-2 in golden hamsters

Abstract

SARS-CoV-2, a novel coronavirus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats, has spread across the world and impacted global healthcare systems and economy 1,2 . A suitable small animal model is needed to support vaccine and therapy development. We report the pathogenesis and transmissibility of the SARS-CoV-2 in golden Syrian hamsters. Immunohistochemistry demonstrated viral antigens in nasal mucosa, bronchial epithelial cells, and in areas of lung consolidation on days 2 and 5 post-inoculation (dpi), followed by rapid viral clearance and pneumocyte hyperplasia on 7 dpi. Viral antigen was also found in the duodenum epithelial cells with viral RNA detected in feces. Notably, SARS-CoV-2 transmitted efficiently from inoculated hamsters to naïve hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was less efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally-infected hamsters showed apparent weight loss, and all animals recovered with the detection of neutralizing antibodies. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in humans with mild infections.SARS-CoV-2 was first detected from a cluster of pneumonia patients in Wuhan, Hubei Province, China in December 2019. Although 55% of the initial cases were linked to one seafood wholesale market where wild animals were also sold 3 , multiple viral (sustained human-to-human transmissibility by symptomatic and pre-symptomatic patients 4 ) and ecological factors (extensive domestic and international travel during Chinese Lunar New Year) have contributed to the rapid global spread of the virus. The clinical spectrum of patients with the novel coronavirus disease (COVID-19) is wide, 19% of 72,314 symptomatic patients in China progressed to severe and critical illness 5 with an estimated 1.4% symptomatic case fatality risk 6 . There is no approved vaccine or treatment against SARS-CoV-2, and the available interventions including country lock-down and social distancing have severely disrupted the global supply chain and economy.A suitable animal model is essential for understanding the pathogenesis of this disease and for evaluating vaccine and therapeutic candidates. Previous animal studies on SARS-CoV suggested the importance of the interaction between the viral spike protein and the host angiotensin converting enzyme 2 (ACE2) receptors 7-10 as well as age and innate immune status of the animals 11-14 in pathogenesis. As with SARS-CoV, the spike protein of SARS-CoV-2 also utilizes ACE2 receptors that are distributed predominantly in the epithelial cells of the lungs and small intestine to gain entry into epithelial cells for viral replication 1,15 . SARS-CoV-2 showed good binding for human ACE2 but limited binding to murine ACE2 1 , which has limited...

Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

“…During the preparation of this manuscript, two publications 5,26 reported SARS-CoV-2 infection and pathogenesis in different transgenic hACE2 expressing mice. Additionally, infectious models in both hamsters 27 , ferrets 11 and nonhuman primates 28 have also been reported. These models are valuable and have provided much-needed tools for the study of SARS-CoV-2 disease.…”

Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife

“…In addition to cats, pangolins 6,7 and hamsters 12 have been reported to be permissive for SARS-CoV-2 infection, however, the target cells for virus infection and putative transmission routes are largely unknown. Our study identified the SARS-CoV-2 target cells in distinct tissues of cat, pangolin and hamster, indicated by the simultaneous expression of SARS-CoV-2 entry factors: ACE2 and TMPRSS2.…”

“…The bat has been proposed to be the original host of SARS-CoV-2 5 , however, the transmission from bats to humans requires some intermediate hosts. Several studies have linked pangolins, cats, dogs and hamsters with SARS-CoV-2 infection and transmission [6][7][8][9][10][11][12] , indicating the potential widespread prevalence across animals, which would post potential threats to humans. The identification of the origin of this virus and its path to becoming a deadly human pathogen is needed to understand how such processes occur in nature and identify ways we can prevent the onset of these types of global crises in the future.…”

Integrate Structural Analysis, Isoform Diversity, and Interferon-Inductive Propensity of ACE2 to Refine SARS-CoV2 Susceptibility Prediction in Vertebrates

“…This concern involves two aspects: (1) screening to identify the animal species that serve as a virus reservoir originally passing SARS-CoV2 to humans; and (2) the existing risk of infected people passing the virus to animals, particularly domestic species, thus potentially amplifying the zoonotic cycle to worsen SARS-CoV2 evolution and prevalence [16,17]. By diagnosis of animals in close contact with COVID-19 patients or screening of animal samples in some COVID-19 epidemic zones, studies detected that domestic cats and dogs could be virally or serologically positive for SARS-CoV2 [18][19][20][21][22][23][24], as was a reported infection in a zoo tiger [25]. Using controlled experimental infection of human SARS-CoV2 isolates, several studies demonstrated that ferrets, hamsters, domestic cats and some non-human primate species are susceptible to human SARS-CoV2 strains [18][19][20][21][22][23][24][25].…”

“…By diagnosis of animals in close contact with COVID-19 patients or screening of animal samples in some COVID-19 epidemic zones, studies detected that domestic cats and dogs could be virally or serologically positive for SARS-CoV2 [18][19][20][21][22][23][24], as was a reported infection in a zoo tiger [25]. Using controlled experimental infection of human SARS-CoV2 isolates, several studies demonstrated that ferrets, hamsters, domestic cats and some non-human primate species are susceptible to human SARS-CoV2 strains [18][19][20][21][22][23][24][25]. Obviously, it is impractical to test SARS-CoV2 susceptibility experimentally in all animal species.…”