Oral SARS-CoV-2 Inoculation Establishes Subclinical Respiratory Infection with Virus Shedding in Golden Syrian Hamsters

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 (10⁵ 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.