SARS-CoV-2 Delta variant induces severe damage in the nasal cavity from the first day post-infection in the Syrian hamster model

SARS-CoV-2 replication initiates in the nasal cavity and can spread to the lower respiratory tract. However, the early physiopathological events that occur in the nasal cavity after infection remain poorly understood. In this study, we investigated the initial steps of viral infection from 1 day post-infection (dpi) in Syrian hamsters infected with SARS-CoV-2 D614G, Delta and Omicron (BA.1) variants and compared them with animals sacrificed at 4dpi. While the level of viral replication in the nasal turbinates of the three groups of hamsters was equivalent at 4dpi, the amount of viral RNA at 1dpi was higher in D614G- and Delta-infected animals than in the Omicron group. No difference in viral RNA levels or inflammatory markers in the nasal turbinates was observed between D614G- and Delta-infected animals, except for a significantly higher level of IFN-γ in the Delta group at 1dpi. Additionally, histological analysis revealed a more rapid diffusion of the Delta virus reaching the posterior zone of the nasal cavity at 1dpi inducing significant damage to the olfactory epithelium. At the same time, the D614G and Omicron infections were essentially restricted to the anterior part of the nasal cavity with less damage observed. Consistently, viral replication was already effective in the lungs of all Delta-infected hamsters at 1dpi, but only in two of the six D614G animals. Our results highlight the importance of studying viral infection in the nasal cavity at early stages of infection with a spatial approach to better understand the physiopathology of the different SARS-CoV-2 variants.