Characterization of Three Variants of SARS-CoV-2in vivoShows Host-Dependent Pathogenicity in Hamsters

Abstract

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron and BA5.2/Omicron, have independent outcomes. We show that in mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected ACE2 mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the ACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data.

SARS-CoV-2 variants of concern exhibit differential gastro-intestinal tropism and pathogenesis in the Syrian golden hamster model

“…The viral burden also started dropping down in the nasal regions at 4 dpi, causing less penetrable to the lungs in the case of Omicron infection at 4 dpi which further explains its lower replication efficiency as opposed to the Delta variant. These data were consistent with earlier observations studied on hamsters (21). The earlier in vitro comparative studies on growth kinetics of the Delta and Omicron variants in Calu3 cells, a lung epithelial cell line, have shown that the Omicron has a poor replication rate which correlates with our findings of low lung viral copy number observed in Omicron infected hamsters (22).…”