Abstract
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, for the first time we established and characterized a direct-contact transmission model for SARS-CoV-2 Omicron BA.5 in hamsters. First, we determined a minimized intranasal dose in a low-volume inoculum required for reproducible infection and viral shedding in male and female hamsters. Next, we determined the optimal co-housing timing and duration between donor and acceptor hamsters required for consistent direct-contact transmission. Finally, we compared viral loads and histopathological lesions in respiratory tissues of donor and acceptor hamsters. Intranasal inoculation of hamsters with 103 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, shedding of infectious virus was significantly higher in male hamsters. Compared to ancestral SARS-CoV-2, Omicron BA.5 infection reached lower viral loads, had a delayed peak of virus replication, and led to less body weight loss. To ensure consistent direct-contact transmission from inoculated donor hamsters to naïve acceptors, a co-housing duration of 24 hours starting 20 hours post infection of the donors was optimal. We detected mild inflammation in the respiratory tract of donor and acceptor hamsters, and viral loads were higher and peaked earlier in donor hamsters compared to acceptor hamsters. Taken together, we developed and characterized a robust Omicron BA.5 direct-contact transmission model in hamsters, that provides a valuable tool to study novel interventions.