期刊
CLINICAL INFECTIOUS DISEASES
卷 71, 期 9, 页码 2428-2446出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciaa325
关键词
coronavirus; COVID-19; SARS-CoV-2; animal; transmission
资金
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government
- Theme-Based Research Scheme of the Research Grants Council, Hong Kong Special Administrative Region [T11/707/15]
- Sanming Project of Medicine in Shenzhen, China [SZSM201911014]
- High Level-Hospital Program, Health Commission of Guangdong Province, China
Background. A physiological small-animal model that resembles COVID-19 with low mortality is lacking. Methods. 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 studies were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titer, chemokine/cytokine level, and neutralizing antibody titer. Results. 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 viral nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked chemokine/cytokine activation were observed within the first week of virus challenge. The mean lung virus titer was between 10(5) and 10(7) TCID50/g. Challenged index hamsters consistently infected naive contact hamsters housed within the same cages, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralizing antibody titers >= 1:427 14 days postchallenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent nonsynonymous adaptive mutation of the spike was found in viruses isolated from the infected hamsters. Conclusions. Besides satisfying Koch's postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.
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