The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster model
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Abstract
The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.
One Sentence Summary
The novel SARS-CoV-2 Omicron variant, though less pathogenic, is highly transmissible and outcompetes the Delta variant under immune selection pressure in the golden Syrian hamster COVID-19 model.
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SciScore for 10.1101/2022.01.12.476031: (What is this?)
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Table 1: Rigor
Ethics IRB: Ethical approvals: The animal experiments were approved by the Institutional Review Board of The University of Hong Kong Committee on the Use of Live Animals in Teaching and Research (CULATR) and the use of clinical specimens was approved by the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster. Sex as a biological variable Briefly, male and female hamsters, aged 8-10 weeks old, were obtained from the Chinese University of Hong Kong Laboratory Animal Service Centre through the HKU Centre for Comparative Medicine Research. Randomization Gender- and age-matched hamsters were randomized into different experimental groups. Blinding titers, … SciScore for 10.1101/2022.01.12.476031: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethical approvals: The animal experiments were approved by the Institutional Review Board of The University of Hong Kong Committee on the Use of Live Animals in Teaching and Research (CULATR) and the use of clinical specimens was approved by the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster. Sex as a biological variable Briefly, male and female hamsters, aged 8-10 weeks old, were obtained from the Chinese University of Hong Kong Laboratory Animal Service Centre through the HKU Centre for Comparative Medicine Research. Randomization Gender- and age-matched hamsters were randomized into different experimental groups. Blinding titers, cytokine/chemokine gene copies, body weights and clinical scores, no blinding procedures were applied to the experimentalists involved. Power Analysis The group sizes were chosen based on statistical power analysis and our prior experience in examining virus burdens and cytokine/chemokine profiles in hamsters. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The plates were then washed 6 times, rabbit anti-hamster horseradish peroxidase antibody (100 μL/well) at the dilution of 1:2000 was added and incubated for 30 min at 37°C. anti-hamstersuggested: (LSBio (LifeSpan Cat# LS-C61251-2000, RRID:AB_1512928)Experimental Models: Cell Lines Sentences Resources Calu-3 and VeroE6-TMPRSS2 cells were maintained in DMEM culture medium supplemented with 10% heat-inactivated FBS, 50 U/ml penicillin and 50 μg/ml streptomycin. VeroE6-TMPRSS2suggested: NoneEqual PFUs of two variants (1:1 ratio) were inoculated onto Calu-3 cells at a final MOI of 0.10 for each variant. Calu-3suggested: BCRJ Cat# 0264, RRID:CVCL_0609)Cell cytopathic effects (CPE) were monitored to validate complete inactivation using Vero cells. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources Statistical analysis: All data were analysed with GraphPad Prism software (GraphPad Software, Inc). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Illustrations: The hamster illustrations and schematic figures were created with BioRender software (https://biorender.com/). BioRendersuggested: (Biorender, RRID:SCR_018361)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study had limitations. The transmission rate of SARS-CoV-2 may vary according to different durations of exposure. In this study, we selected 6 hours of non-contact transmission to simulate the scenarios of staying with an infected index patient within the same facility for a routine business day and on medium-haul flights. It would be worthwhile to further compare the transmissibility of the Omicron and other variants after different durations of exposure in future studies. It would also be important to investigate the pathogenicity and transmissibility of the Omicron variant in additional animal models such as the hACE2-transgenic mouse and non-human primate models, as each of these animal models have their advantages and disadvantages in recapitulating human disease. In summary, the present study shows that despite comparatively lower pathogenicity than the Delta variant, the Omicron variant undoubtedly still causes obvious clinical effects, increased viral burdens and pro-inflammatory cytokines/chemokines, as well as histopathological damages in infected hosts. Taking into consideration the Omicron variant’s higher transmissibility than the already-highly transmissible Delta variant, our findings highlight the urgent need to find next-generation COVID-19 vaccines and broad-spectrum therapeutics, as well as to tighten non-pharmaceutical measures to reduce acute and chronic disease burden (long COVID) on the public and healthcare facilities.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
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Results from scite Reference Check: We found no unreliable references.
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