Histopathologic Characterization of Experimental Peracute SARS-CoV-2 Infection in the Syrian Hamster

SIMPLE SUMMARY: Understanding how a virus interacts with cellular targets in an animal model provides critical information in developing therapeutic targets and vaccines for humans. The Syrian hamster model of SARS-CoV-2 infection, the causative agent of COVID-19, is one of the most widely used animal models for this disease. While extensive work on vaccine and therapeutic interventions have been performed in this animal model, the initial viral targets and spread throughout the respiratory tract has been poorly documented. We sought to evaluate the viral spread by microscopic examination of tissues as early as 6 hours post intranasal inoculation through the development of lung lesions at 3 days post inoculation. ABSTRACT: Coronavirus Infectious Disease 2019 (COVID-19) initiated a global pandemic that thus far has resulted in the death of over 6.5 million people internationally. Understanding the viral tropism during the initial, subclinical phase of infection is critical to develop targeted vaccines and therapeutics. With the continued emergence of variants of concern, particularly those that appear to have a tropism for the upper respiratory tract, understanding the complete pathogenesis is critical to develop more effective interventions. Thus far, the Syrian hamster has served as the most consistent small animal model of SARS-CoV-2 infection for mild to moderate respiratory disease. Herein, we utilize histopathology and immunohistochemistry to characterize the peracute phase of disease initiating at 6-h-post-inoculation in the intranasal inoculation route Syrian hamster model. Inflammation and viral replication initiates in the respiratory epithelium of nasal turbinates as early as 12-h-post-inoculation and moves caudally through the nasal cavity by 36-h-post inoculation. Lower respiratory involvement can be detected as early as 12-h-post inoculation in the intranasal inoculated hamster model. These data highlight the importance of rostral nasal cavity sampling at early timepoints for detection of SARS-CoV-2 in the Syrian hamster model.