Virology: Ability of Omicron to replicate and cause disease in mice investigated

Insights into the reduced ability of the Omicron variant of SARS-CoV-2 to replicate and cause disease in cells and a mouse model, compared to other variants of concern, are presented in a paper published in Nature.

Kwok-Yung Yuen and colleagues investigated the replication efficacy and pathogenicity of Omicron in a series of cell and mouse models. In laboratory experiments in human lung and intestinal epithelial cells, the authors found that replication of the live Omicron virus was reduced compared to the original strain of SARS-CoV-2 (wild type) and the Alpha, Beta and Delta variants. In human lung epithelial cells, Omicron was more than three times less efficient at replicating compared to wild-type virus. By contrast, Alpha, Beta and Delta replicated at similar or higher levels than the wild type.

Further investigations revealed that Omicron inefficiently uses the cell membrane protein transmembrane serine protease 2 (TMPRSS2), which mediates viral entry in certain cells. The authors suggest that mutations in the spike protein of Omicron may reduce its capacity to use the TMPRSS2 pathway, impairing its entry and replication in the human epithelial cell lines.

In a mouse model, replication of Omicron was reduced in both the upper and lower respiratory tract compared to the wild type and Delta. An analysis of the lung tissue revealed that infection with Omicron resulted in reduced levels of inflammation and damage in the lungs compared to the wild type and Delta. This was also associated with lower body weight loss and improved animal survival compared to other variants of concern.