Prolonged dysregulation and pathological changes in the upper respiratory tract of SARS-CoV-2 infected hamsters.

Respiratory long COVID symptoms, including dyspnea and breathing pattern disorders, are frequently reported in convalescent COVID-19 patients. Yet the mechanisms driving these persistent respiratory manifestations remain poorly elucidated. In this study, we characterized persistent upper respiratory tract pathology in SARS-CoV-2-infected hamsters. Strikingly, we observed persistent expression of SARS-CoV-2 nucleocapsid (N) protein and subgenomic RNA (sgRNA) gene, which resulted in sustained tissue pathologies, dysregulation of pro-inflammatory markers, pro-apoptotic genes, as well as the altered expression of viral entry receptors, in the nasal turbinate of infected hamsters up to 120 days post-infection. These findings indicate that residual viral components may contribute to dysregulation of tissue repair and remodeling, chronic tissue pathology, and potentially enhanced susceptibility to secondary respiratory infections upon SARS-CoV-2 infection even upon recovery of acute infection. Collectively, our study provides insights into potential drivers of post-acute COVID-19 sequelae in the upper respiratory tract.