Reduced Pathogenicity of the SARS-CoV-2 Omicron Variant in Hamsters

Abstract

The SARS-CoV-2 Omicron (B.1.1.529) variant has proven 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. 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, as expected. 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 still led to substantial viral replication in both the upper and lower respiratory tracts and pulmonary pathology, but with a trend towards higher viral loads in nasal turbinates and lower viral loads in lung parenchyma compared with WA1/2020 infection. These data suggest that the SARS-CoV-2 Omicron variant may result in more robust upper respiratory tract infection but less severe lower respiratory tract clinical disease compared with prior SARS-CoV-2 variants.

Pathogenicity of SARS-CoV-2 Omicron in Syrian hamsters and its neutralization with different Variants of Concern

“…The disease characteristics of the Omicron variant observed here are similar to those reported for other SARS-CoV-2 variants like Alpha, Beta, Kappa and Delta in hamsters by earlier studies except that of the body weight loss [9,19,32,33]. Our finding corroborated with the few recent studies which also reported the limited or negligible body weight loss in hamsters post infection with Omicron variants [22][23][24][25][26]. The age and virus dose can affect the body weight loss and disease severity in hamsters post SARS-CoV-2 infection [20,32].…”

“…We have used 5-6 week old hamsters and other published studies on Omicron infection in Syrian hamsters have also used animals of the age range of 4 to 8 weeks except Ryan et al, have used 20-22 week animals [22]. Even high Omicron virus doses could not result in body weight loss in hamsters [23]. In the present study we have used only a single dose for virus infection.…”

Milder disease with Omicron: is it the virus or the pre-existing immunity?

“…This is important as it will restrict the virus to the upper respiratory tract where TMPRESS2-independent, cell-free transmission drives infection, and makes it less likely to spread in the lungs, where cell fusion plays a stronger role in viral transmission and the damage from infection is more serious. This observation is supported by studies in Syrian hamsters and human ACE2-expressing mice, which found that Omicron infection causes milder lung pathology 5 , 6 . The studies also show that the weight of the infected animals, which decreases by about 10% with Delta infection, does not go down with Omicron infection as much (mice) or at all (hamsters).…”

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

“…leads to a lower hospitalization rate with Omicron infection (https://www.discovery.co.za/corporate/health-insights-vaccines-real-world-effectiveness). This may be because Omicron does not have extensive escape from other arms of the adaptive immune response 12 or because Omicron virus shows attenuated cell-to-cell spread 13 which leads to decreased lung infection and pathology 14,15 . A stronger neutralizing response after Omicron infection, as shown here in vaccinated participants, should also contribute to vaccine mediated protection against more severe disease with Omicron.…”