Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron

Area of Science:

• Virology
• Pathology
• Immunology

Background:

• The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged rapidly in November 2021.
• While Omicron demonstrates immune escape from neutralization antibodies, its pathogenicity is not well understood.

Purpose of the Study:

• To investigate the pathogenicity and replication efficiency of the SARS-CoV-2 Omicron variant.
• To compare Omicron's characteristics with wild-type SARS-CoV-2 and other variants.

Main Methods:

• In vitro replication assays in human Calu3 and Caco2 cells.
• In vivo studies using K18-hACE2 mice infected with Omicron, wild-type, Delta, Alpha, and Beta variants.
• Assessment of viral replication in respiratory tracts, lung pathology, body weight reduction, and mortality rates.

Main Results:

• Omicron replication was substantially attenuated in human lung cells (Calu3, Caco2) and the respiratory tracts of K18-hACE2 mice.
• Omicron showed inefficient use of transmembrane serine protease 2 (TMPRSS2) compared to other SARS-CoV-2 strains.
• Infection with Omicron resulted in significantly ameliorated lung pathology, lowest body weight reduction, and lowest mortality rate in mice compared to wild-type and other variants.

Conclusions:

• The Omicron variant exhibits attenuated replication and pathogenicity in vivo.
• Reduced TMPRSS2 utilization may contribute to Omicron's attenuated phenotype.
• Omicron presents a less severe disease profile in a mouse model compared to previous SARS-CoV-2 variants.