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

  1. Sreelekshmy Mohandas
  2. Pragya D. Yadav
  3. Gajanan Sapkal
  4. Anita M. Shete
  5. Gururaj Deshpande
  6. Dimpal A. Nyayanit
  7. Deepak Patil
  8. Manoj Kadam
  9. Abhimanyu Kumar
  10. Chandrashekhar Mote
  11. Rajlaxmi Jain

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Abstract

SARS-CoV-2 Omicron variant is rampantly spreading across the globe. Animal models are useful in understanding the disease characteristics as well as properties of emerging SARS-CoV-2 variants. We assessed the pathogenicity and immune response generated by BA.1 sub-lineage of SARS-CoV-2 Omicron variant with R346K mutation in 5 to 6-week old Syrian hamsters. Virus shedding, organ viral load, lung disease and immune response generated were sequentially assessed. The disease characteristics of Omicron were found to be similar to that of other SARS-CoV-2 variants of concerns in hamsters like high viral replication in the respiratory tract and interstitial pneumonia. The infected hamsters demonstrated lesser body weight gain in comparison to the uninfected control hamsters. Viral RNA could be detected in nasal washes and respiratory organs (nasal turbinate, trachea, bronchi and lungs) till 10 and 14 days respectively. The clearance of the virus was observed from nasal washes and lungs by day 7. Neutralizing antibody response against Omicron variant was detected from day 5 with rising antibody titers till 14 days. However, the cross-neutralization titre of the sera against other variants showed severe reduction ie., 7 fold reduction against Alpha and no titers against B.1, Beta and Delta. This preliminary data shows that Omicron variant infection can produce moderate to severe lung disease and the neutralizing antibodies produced in response to Omicron variant infection shows poor neutralizing ability against other co-circulating SARS-CoV-2 variants like Delta which necessitates caution as it may lead to increased cases of reinfection.

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  1. ScreenIT

    SciScore for 10.1101/2022.01.19.477013: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: Hamster experiments: The experiment was approved by the Institutional Animal Ethics Committee of ICMR-National Institute of Virology (ICMR-NIV), Pune.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingCoded tissue samples were blindly scored by a pathologist.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 IgG ELISA: The hamster serum samples were tested for antibodies using anti-SARS-CoV-2 hamster IgG ELISA [32] and S1-Receptor Binding Domain (RBD) ELISA.
    Anti-SARS-CoV-2 IgG
    suggested: None
    anti-SARS-CoV-2 hamster IgG
    suggested: None
    S1-Receptor Binding Domain ( RBD
    suggested: None
    Polyclonal anti-SARS-CoV-2 mouse serum (generated in the laboratory using inactivated SARS-CoV-2 antigen in mice) was used as the primary antibody.
    anti-SARS-CoV-2
    suggested: None
    Goat anti-mouse horse radish peroxidase antibody (Dako, USA) and 3, 3’-diaminobenzidine (DAB) tetrahydrochloride substrate were used as secondary antibody and for detection respectively.
    anti-mouse
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The virus titer was found to be 105 TCID50/ml on titration in Vero CCL81 cells as per the Reed and Muench method.
    Vero CCL81
    suggested: None
    The lungs, nasal turbinates and NW samples were titrated for the live virus in Vero CCL-81 cells (ATCC, USA) to determine the presence of replication competent virus as described earlier [15].
    Vero CCL-81
    suggested: None
    Software and Algorithms
    SentencesResources
    Data analysis: The experimental data was analyzed using Graph pad Prism version 9.2.0 software.
    Graph pad Prism
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.01.19.477013v1 on bioRxiv