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 were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titre, chemokine/cytokine assay, and neutralising antibody titre. 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 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. Conclusions 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.

Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium-to-large sized respiratory droplets although airborne transmission is theoretically possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19. Methods We used a well-established golden Syrian hamster SARS-CoV-2 model. We placed SARS-CoV-2-challenged index hamsters and naïve hamsters into closed system units each comprising two different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed in between the cages was investigated. Besides clinical scoring, hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression. Results Non-contact transmission was found in 66.7% (10/15) of exposed naïve hamsters. Surgical mask partition for challenged index or naïve hamsters significantly reduced transmission to 25% (6/24, P=0.018). Surgical mask partition for challenged index hamsters significantly reduced transmission to only 16.7% (2/12, P=0.019) of exposed naïve hamsters. Unlike the severe COVID-19 manifestations of challenged hamsters, infected naïve hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues. Conclusions SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei in the hamster model. Such transmission could be reduced by surgical mask usage, especially when masks were worn by infected individuals.

This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Summary Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is transmitted largely by respiratory droplets or airborne aerosols. Despite being frequently found in the immediate environment and feces of patients, evidence supporting the oral acquisition of SARS-CoV-2 is unavailable. Using the Syrian hamster model, we demonstrate that the severity of pneumonia induced by the intranasal inhalation of SARS-CoV-2 increases with virus inoculum. SARS-CoV-2 retains its infectivity in vitro in simulated human-fed-gastric and fasted-intestinal fluid after 2 h. Oral inoculation with the highest intranasal inoculum (10 5 PFUs) causes mild pneumonia in 67% (4/6) of the animals, with no weight loss. The lung histopathology score and viral load are significantly lower than those infected by the lowest intranasal inoculum (100 PFUs). However, 83% of the oral infections (10/12 hamsters) have a level of detectable viral shedding from oral swabs and feces similar to that of intranasally infected hamsters. Our findings indicate that the oral acquisition of SARS-CoV-2 can establish subclinical respiratory infection with less efficiency.

The in vivo pathogenicity, transmissibility, and fitness of the SARS-CoV-2 Omicron (B.1.1.529) variant are unclear. We compared these virological attributes of this new variant of concern with those of the Delta (B.1.617.2) variant in a Syrian hamster model of COVID-19. Omicron-infected hamsters lost significantly less body weight and exhibited reduced clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and lung damage than Delta-infected hamsters. Both variants were highly transmissible via contact transmission. In non-contact transmission studies, Omicron demonstrated similar or higher transmissibility than Delta. Delta outcompeted Omicron without selection pressure. This scenario drastically changed once immune selection pressure with neutralizing antibodies active against Delta but poorly active against Omicron was introduced. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.