Maya Naghibosadat, Sunnybrook Research Institute/ University of Toronto

Maya Naghibosadat1, Elan Hahn4 , George Babuadze2*, Robert Kozak1,3* 1. Biological Sciences, Sunnybrook Research Institute, Sunnybrook Hospital, Toronto, Canada 2. University of Texas Medical Branch, Galveston, Texas, USA. 3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 4. Mount Sinai Hospital, Toronto, Canada

Damaging & Spreading

Background: The SARS-CoV-2 pandemic has caused millions of infections, with some individuals developing long COVID, a condition characterized by persistent symptoms. Understanding its pathophysiology is essential for developing treatments. Investigating disease progression associated with different variants is crucial for understanding long COVID pathology. Syrian golden hamsters serve as a suitable model due to their transient yet non-lethal disease phenotype. To investigate variant-specific pathology, we challenged Syrian golden hamsters with different SARS-CoV-2 variants and assessed organ pathology in the convalescent phase. Methods: Male Syrian golden hamsters (4–6 weeks old) were intranasally challenged with 1.78 × 10⁶ TCID₅₀ of SARS-CoV-2 variants, including WT (B1), B.1.1.7 (Alpha), and B.1.351 (Beta). Hamsters (n=10 per group) were monitored for 28 days for clinical signs and viral shedding. Lungs, nasal turbinates, heart, kidneys, and spleens were collected at 14- and 28-days post-infection for quantitative histopathological analysis. Results & Conclusion: All variants produced similar acute disease, with peak viral loads on day 3 and maximal weight loss on day 7. Inflammation and fibrosis were evident in every infected group. WT and Alpha variants caused greater lung, cardiac, and renal fibrosis than Beta, while splenic germinal-center expansion was most pronounced in Alpha. These findings establish that SARS-CoV-2 leaves variant-dependent post-acute multi-organ damage in hamsters, with WT and Alpha inducing the most severe pathology. This model captures variant-dependent post-acute organ injury and provides a quantitative framework for evaluating anti-fibrotic interventions. Further studies are ongoing to characterize these pathological differences and elucidate the underlying mechanisms contributing to these observations.