Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility
Top Cited Papers
Open Access
- 26 March 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 71 (9), 2428-2446
- https://doi.org/10.1093/cid/ciaa325
Abstract
A physiological small animal model that resembles COVID-19 with low mortality is lacking. Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titre, chemokine/cytokine assay, and neutralising antibody titre. The Syrian hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with virus nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked cytokine activation were observed within the first week of virus challenge. The lung virus titre was between 105-107 TCID50/g. Challenged index hamsters consistently infected naïve contact hamsters housed within the same cage, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralising antibody titre ≥1:427 fourteen days post-challenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent non-synonymous adaptive mutation of the spike was found in viruses isolated from infected hamsters. Besides satisfying the Koch’s postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.Keywords
Funding Information
- Sanming Project of Medicine in Shenzhen, China (SZSM201911014)
- High Level-Hospital Program, Health Commission of Guangdong Province, China
This publication has 32 references indexed in Scilit:
- Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like DiseaseClinical Microbiology Reviews, 2015
- Rodent NutritionVeterinary Clinics of North America: Exotic Animal Practice, 2014
- Two Years after Pandemic Influenza A/2009/H1N1: What Have We Learned?Clinical Microbiology Reviews, 2012
- Duplex real-time reverse transcriptase PCR to determine cytokine mRNA expression in a hamster model of New World cutaneous leishmaniasisBMC Immunology, 2010
- Gene selection algorithm by combining reliefF and mRMRBMC Genomics, 2008
- Macromolecular Modeling with RosettaAnnual Review of Biochemistry, 2008
- I-TASSER server for protein 3D structure predictionBMC Bioinformatics, 2008
- Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging InfectionClinical Microbiology Reviews, 2007
- Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian HamstersJournal of Virology, 2005
- MUSCLE: multiple sequence alignment with high accuracy and high throughputNucleic Acids Research, 2004