Reduced pathogenicity of the SARS-CoV-2 omicron variant in hamsters.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant has proven to be highly transmissible and has outcompeted the Delta variant in many regions of the world. Early reports have also suggested that Omicron may result in less severe clinical disease in humans. Here, we show that Omicron is less pathogenic than prior SARS-CoV-2 variants in Syrian golden hamsters. Methods: Hamsters were inoculated with either SARS-CoV-2 Omicron or other SARS-CoV-2 variants. Animals were followed for weight loss, and upper and lower respiratory tract tissues were assessed for viral loads and histopathology. Findings: Infection of hamsters with the SARS-CoV-2 WA1/2020, Alpha, Beta, or Delta strains led to 4%-10% weight loss by day 4 and 10%-17% weight loss by day 6. In contrast, infection of hamsters with two different Omicron challenge stocks did not result in any detectable weight loss, even at high challenge doses. Omicron infection led to substantial viral replication in both the upper and lower respiratory tracts but demonstrated lower viral loads in lung parenchyma and reduced pulmonary pathology compared with WA1/2020 infection. Conclusions: These data suggest that the SARS-CoV-2 Omicron variant may result in robust upper respiratory tract infection, but less severe lower respiratory tract clinical disease, compared with prior SARS-CoV-2 variants. Funding: Funding for this study was provided by NIH grant CA260476, the Massachusetts Consortium for Pathogen Readiness, the Ragon Institute, and the Musk Foundation.

Vaccine protection against the SARS-CoV-2 Omicron variant in macaques.

The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers and undetectable Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Moreover, virologic control correlated with both antibody and T cell responses. These data suggest that both humoral and cellular immune responses contribute to vaccine protection against a highly mutated SARS-CoV-2 variant.