Comparative infection and pathogenesis of SARS-CoV-2 Omicron and Delta variants in aged and young Syrian hamsters

  1. Nadia Storm
  2. Nicholas A. Crossland
  3. Lindsay G. A. McKay
  4. Anthony Griffiths

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Abstract

Coronavirus disease 2019 continues to batter the world with the unceasing introduction of new variants of the causative virus, SARS-CoV-2. In order to understand differences in disease caused by variants of concern and to develop variant-specific vaccines, suitable small animal models are required that mimic disease progression in humans at various stages of life. In this study, we compared the dynamics of infection with two SARS-CoV-2 variants of concern (Delta and Omicron) in aged (>1 year 3 months old) and young (<5 weeks old) Syrian hamsters ( Mesocricetus auratus ). We show that no weight loss occurred in Omicron infected groups regardless of age, while infection with the Delta variant caused weight loss of up to 10% by day 7 post-infection with slower and incomplete recovery in the aged group. Omicron replicated to similar levels as Delta in the lungs, trachea and nasal turbinates, with no significant differences in the tissue viral loads of aged versus young animals for either variant. In contrast to rare necrosis observed in Omicron-infected animals regardless of age, severe necrosis was observed in the olfactory epithelium in Delta-infected animals. Omicron infection also resulted in mild pulmonary disease in both young and aged animals compared to the moderate acute necrotizing bronchointerstitial pneumonia seen in Delta-infected animals. These results suggest that Omicron infection results in an attenuated clinical disease outlook in Syrian hamsters compared to infection with the Delta variant irrespective of age.

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  1. Version published to 10.1101/2022.03.02.482662v2 on bioRxiv
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    SciScore for 10.1101/2022.03.02.482662: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: Approval for this study was obtained from the Boston University Institutional Biosafety Committee (IBC) and Institutional Animal Care and Use Committee (
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingSlides were examined blinded by a board-certified veterinary pathologist (N.A.C.), with subsequent unblinding conducted to generate pathology results.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The dilutions were then plated onto Vero E6 cells seeded at 8 × 105 cells per well (NR-596, BEI Resources).
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    The half maximal inhibitory concentration (IC50) for each serum sample was determined from dose response curves constructed in GraphPad Prism 8.4.2.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical Analysis: Data were prepared and analyzed using GraphPad Prism 8.4.2 software (GraphPad Software Inc., California, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, this model is not without limitations. It has been established that severe COVID-19 disease is associated with one or more co-morbidities (Zhou et al., 2020) which is not readily reproducible in animals, representing a challenge in developing models that fully represent the more severe manifestation of the disease. Our findings illustrate that weight loss was more pronounced and recovery incomplete in aged animals infected with the Delta variant compared to young animals. These findings are consistent with a previous study comparing infection with an early variant of SARS-CoV-2 (BetaCoV/Germany/BavPat1/2020) in aged and young Syrian hamsters (Osterrieder et al., 2020) where weight loss was more distinct in older animals. Infection with Omicron did not result in weight loss in animals in either cohort. Omicron replicated to similar levels as Delta in the upper respiratory tract (nasal turbinates and trachea) with a trend towards decreased viral load in the lower respiratory tract (lungs) during acute disease (3 DPI), with no significant differences in tissue viral loads of aged versus young animals for either variant. In contrast, histopathologic differences were clear among the Omicron and Delta variants in both the nasal passages and lungs. Specifically, severe necrosis was observed acutely (3 DPI) in the OE of Delta-infected animals, while this phenotype was either absent or mild and segmental in Omicron-infected animals regardless of age. Acute Omicron infection (...

    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.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.03.02.482662v1 on bioRxiv