Characterization of a SARS-CoV-2 Omicron BA.5 direct-contact transmission model in hamsters

As SARS-CoV-2 continues to evolve antigenically to escape vaccine- or infection-induced immunity, suitable animal models are needed to study novel interventions against viral variants. Syrian hamsters are often used because of their high susceptibility to SARS-CoV-2 and associated tissue damage in the respiratory tract. Here, we established a direct-contact transmission model for SARS-CoV-2 Omicron BA.5 in hamsters. First, we determined whether 10³ or 10⁴ TCID₅₀ in a low-volume inoculum led to reproducible infection and viral shedding in male and female hamsters. Next, we determined the optimal co-housing timing and duration between donor and recipient hamsters required for consistent direct-contact transmission. Finally, we compared viral loads and histopathological lesions in the respiratory tissues of donor and recipient hamsters. Intranasal inoculation of hamsters with 10³ TCID₅₀ and 10⁴ TCID₅₀ Omicron BA.5 in 10 µl per nostril led to reproducible infection. Viral loads in the throat measured by RT-qPCR were comparable between male and female hamsters. Notably, the shedding of infectious virus was significantly higher in male hamsters. Compared to SARS-CoV-2 D614G, Omicron BA.5 infection reached lower viral loads, had a delayed peak of virus replication, and induced limited body weight loss. To ensure consistent direct-contact transmission from inoculated donor hamsters to naïve recipients, a co-housing duration of 24 h starting 20 h post-infection of the donors was optimal. We detected mild inflammation in the respiratory tract of donor and recipient hamsters, and viral loads were higher and peaked earlier in donor hamsters compared to recipient hamsters. Taken together, we developed a robust Omicron BA.5 direct-contact transmission model in hamsters, that provides a valuable tool to study novel interventions.