Study investigates the virological attributes of Omicron in a Syrian hamster model

By Neha MathurReviewed by Danielle Ellis, B.Sc.Jun 27 2022

In a recent study published in the Science, researchers investigated the virological attributes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) new variant of concern (VOC) Omicron in a Syrian hamster model.

Background

SARS-CoV-2 VOC Omicron has emerged as the dominant circulating SARS‐CoV‐2 variant. It evades immunity and has subsequently made currently used anti-SARS-CoV-2 therapeutic monoclonal antibodies and vaccine-induced neutralizing antibodies (nAbs) futile. However, little is known about Omicron’s in vivo virology, transmissibility, and fitness.

Under in vitro conditions, the Delta VOC has shown a significant fitness advantage over Omicron for up to 72 hours post-infection (hpi). However, selection pressure by vaccinated sera containing anti-Delta nAbs helped Omicron outcompete Delta.

About the study

In the present study, the authors validated their own in vitro findings using a Syrian hamster model of coronavirus disease 2019 (COVID‐19). They compared the virological attributes of the SARS-CoV-2 Delta (B.1.617.2) variant with the Omicron (B.1.1.529) variant under in vivo conditions. To investigate how Omicron outcompeted Delta in vivo, the team intranasally challenged non-vaccinated and vaccinated Syrian hamsters with the Delta and Omicron variants in a 1:1 ratio. Next, the researchers directly compared the transmissibility of Omicron and Delta in vivo. For this, they co-housed six index SARS-CoV-2-challenged hamsters with six naïve hamsters in a 1:1 ratio.

The team also randomly divided 42 hamsters into six groups of the index and naïve hamsters in a non-contact transmission system. They exposed all index hamsters to high nasal wash virus titers at one day post-infection (dpi); subsequently, 83.3% of Omicron-exposed and 66.7% of Delta-exposed naïve hamsters contracted the infection.

Study findings

The vaccinated hamsters showed waning serum antibody responses at 28 days post-vaccination; consequently, their serum had anti-SARS-CoV-2 nAbs, which were more active against Delta but poorly active against Omicron. In the non-vaccinated hamsters, Delta outcompeted Omicron, whereas Omicron had a fitness advantage over Delta in the vaccinated hamsters. Thus, Delta exhibited a fitness advantage over Omicron in the absence of immune selection pressure; however, the scenario drastically changed once the researchers introduced selection pressure by vaccinating the test animals. It explains how Omicron became dominant and replaced Delta as the circulating SARS-CoV-2 VOC.

The researchers observed that Omicron-infected animals showed <5% weight reduction and lower clinical scores. Omicron had a similar infectious titer as Delta in the nasal turbinate and trachea in the early infection stage; however, it replicated lesser in the lungs at two dpi. In addition, the viral burden of Omicron remained consistently lower than that of Delta throughout the upper and lower respiratory tract. Further, Omicron induced much less lung tissue damage and reduced cytokine and chemokine dysregulation.

Furthermore, the Omicron-infected hamsters had a lower histological score between two and seven dpi. The lungs of these animals had alveolar wall congestion but much less severe and diffused compared to Delta-infected hamsters. The lung damage resolved quicker in the Omicron-infected hamsters, and they had less abundant viral nucleocapsid protein expression. Overall, Omicron exhibited weaker pathogenicity in vivo compared to Delta.

Under in vitro conditions, the Omicron spike showed reduced receptor binding, fusogenicity, and S1 subunit shedding. Moreover, it showed reduced replication compared with Delta inside human lungs-derived Calu-3 cells, as assessed via live virus assays. Conversely, under ex vivo conditions, Omicron exhibited enhanced replication in the bronchi compared with Delta. In striking contrast, recent animal studies showed that Omicron is less replicative than Delta throughout the upper and lower respiratory tract.

Omicron exhibited similar or higher transmissibility than Delta via contact and non-contact transmissions, despite having lower respiratory tract viral loads. Although results did not reach a statistical significance, the Omicron transmission rate was consistently around 10% to 20% higher than Delta.

Conclusions

Recent epidemiological studies have shown that Omicron spreads 4.2 times faster than Delta in its early stage. Its reproduction time (R_t) was found to be between 2.5 to 3.7 in South Africa and the United Kingdom, respectively, with a doubling time of three days. Omicron is also rapidly spreading in vaccinated populations, also among those who have received two-dose COVID-19 vaccination. However, whether this is due to Omicron’s intrinsic transmissibility or environmental/social factors is unknown.

Nevertheless, there is an urgent need for next-generation COVID-19 vaccines and antiviral treatments which could effectively combat Omicron and other SARS-CoV-2 variants which might evolve in the future. Future studies should investigate other aspects of Omicron infectiousness and transmissibility. For instance, its ability to enter host cells, stick to inanimate surfaces, and ability to transmit via aerosols.