Differential olfactory dysfunction and nasal tissue pathology in Syrian hamsters infected with SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, frequently induces olfactory dysfunction (OD), a symptom that significantly impacts patients' quality of life. Understanding the variability in OD and nasal tissue pathology across different SARS-CoV-2 variants may provide insights as to the mechanisms underlying this symptom and inform therapeutic strategies for COVID-19-related sequelae. This study examines the OD and associated nasal pathology in Syrian hamsters infected with SARS-CoV-2 variants, including Wuhan (WA-1), Alpha, Beta, Gamma, Delta, and Omicron, at 5 days post-infection. Olfactory function was assessed using buried food detection tests. Hamsters infected with the WA-1, Alpha, Beta, and Gamma variants exhibited prolonged discovery times as compared to controls, indicating severe OD. In contrast, those infected with the Delta and Omicron variants showed minimal or mild delays. Pathological examination of the lateral turbinate (LT) revealed severe olfactory epithelial damage in WA-1, Alpha, Beta, Gamma, and Delta variant infections, while the Omicron variant caused minimal damage. Viral antigens were detected in retained and/or sloughed epithelial cells in the LT across all variant infections. These results demonstrate significant differences in OD severity and nasal tissue damage among SARS-CoV-2 variants, providing critical insights for understanding the pathogenesis of this symptom and guiding treatment development for COVID-19 sequelae.IMPORTANCEOlfactory dysfunction (OD) is a prominent and distinctive symptom of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection that significantly affects patients' quality of life. This study reveals that Syrian hamsters infected with different SARS-CoV-2 variants (WA-1, Alpha, Beta, Gamma, Delta, and Omicron) exhibit varying degrees of OD and nasal tissue pathology. Hamsters infected with the WA-1, Alpha, Beta, and Gamma variants experienced significant OD, while those infected with Delta and Omicron showed milder symptoms. Severe epithelial damage in the nasal turbinate was observed in hamsters infected with WA-1, Alpha, Beta, Gamma, and Delta variants, whereas Omicron variant infection resulted in minimal tissue injury. Despite the variability in OD and tissue damage, viral antigen was detected in all infected hamsters. These findings underscore the diverse impact of SARS-CoV-2 variants on olfactory function and nasal tissue pathology, providing important insights into the pathogenesis of OD and guiding potential therapeutic strategies for coronavirus disease 2019-related olfactory sequelae.