Oral SARS-CoV-2 inoculation leads to distinct viral distribution compared to nasal inoculation in a Syrian hamster model.

Abstract

OBJECTIVES: The nose and mouth are the primary entry points for upper respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the influence of different entry routes on viral spread remains unclear. Oral and nasal infection routes in terms of viral distribution and presence of inflammation were compared. METHODS: Syrian hamsters were inoculated with SARS-CoV-2 via three routes: nasal inoculation (NI), simulating conventional upper respiratory infection; lingual (supra-lingual) inoculation (LI), simulating exposure during speaking and eating; and sublingual inoculation (SI), simulating exposure to the salivary glands. After three days, the lungs, submandibular glands, nasal turbinates, liver, and brain were examined histologically and immunohistochemically. To assess direct access to the lungs, India ink was administered via each route and analyzed after tissue clearing. RESULTS: NI resulted in infection in the nasal olfactory sensory epithelium of the nasal cavity and in the lungs. India ink studies suggest that the virus is likely to have infected the nasal mucosa first, followed by secondary infection of the lungs. LI resulted in marked infection of the submandibular glands with vascular involvement. In the LI and SI groups, no viral antigen was detected in the lungs; however, there was inflammation of the lungs, suggesting cytokine-mediated effects. CONCLUSION: Different upper respiratory entry routes produced distinct pathological patterns. While nasal infection is well recognized, our findings indicate that salivary gland infection via SI may suggest an alternative pathway for systemic viral dissemination.