SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant

  1. Pragya D. Yadav
  2. Sreelekshmy Mohandas
  3. Anita M Shete
  4. Dimpal A Nyayanit
  5. Nivedita Gupta
  6. Deepak Y. Patil
  7. Gajanan N. Sapkal
  8. Varsha Potdar
  9. Manoj Kadam
  10. Abhimanyu Kumar
  11. Sanjay Kumar
  12. Deepak Suryavanshi
  13. Chandrashekhar S. Mote
  14. Priya Abraham
  15. Samiran Panda
  16. Balram Bhargava

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Abstract

Background

The recent emergence of new SARS-CoV-2 lineage B.1.617 in India has been associated with a surge in the number of daily infections. This variant has combination of specific mutations L452R, E484Q and P681R reported to possibly enhance the transmissibility with likelihood of escaping the immunity. We investigated the viral load and pathogenic potential of B.1.617.1 in Syrian golden hamsters.

Methods

Two groups of Syrian golden hamsters (9 each) were inoculated intranasally with SARS CoV-2 isolates, B.1 (D614G) and B.1.617.1 respectively. The animals were monitored daily for the clinical signs and body weight. The necropsy of three hamsters each was performed on 3, 5- and 7-days post-infection (DPI). Throat swab (TS), nasal wash (NW) and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2 specific Real-time RT-PCR.

Results

The hamsters infected with B.1.617.1 demonstrated increased body weight loss compared to B.1 variant. The highest viral load was observed in nasal turbinate and lung specimens of animals infected with B.1.167.1 on 3 DPI. Neutralizing antibody (NAb) and IgG response in hamsters of both the groups were observed from 5 and 7 DPI respectively. However, higher neutralizing antibody titers were observed against B.1.167.1. Gross pathology showed pronounced lung lesions and hemorrhage with B.1.671 compared to B.1.

Conclusions

B.1617.1 and B.1 variant varied greatly in their infectiousness, pathogenesis in hamster model. This study demonstrates higher pathogenicity in hamsters evident with reduced body weight, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant.

Summary

B.1.617.1 is the new SARS-CoV-2 lineage that emerged in India. Maximal body weight loss and higher viral load in hamsters infected with B.1.617.1. It caused pronounced lung lesions in hamsters compared to B.1 variant which demonstrates the pathogenic potential of B.1.617.1.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.05.442760: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: Ethics statement: The animal experiments were performed with the approval of the Institutional Animal Ethics committee and all the experiments were performed as per the guidelines of CPSCEA (NIV/IAEC/2021/MCL/01).
    Euthanasia Agents: ) (GISAID number: EPI_ISL_420545) and B.1.617.1 (GISAID number: EPI_ISL_1669767) lineages propagated at ICMR-NIV, Pune as described earlier under isoflurane anesthesia [9,13].
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Virus titration: The lungs and nasal turbinate samples were used for virus titration in Vero CCL-81 cells.
    Vero CCL-81
    suggested: None
    Software and Algorithms
    SentencesResources
    Real-time RT-PCR: Nasal wash and TS collected in 1ml viral transport medium and weighed organ samples (lungs, nasal turbinate and trachea) triturated in 1 ml media were used for RNA extraction using MagMAX™
    MagMAX™
    suggested: None
    Statistical analysis: Graphpad Prism version 8.4.3 software was used to assess the statistical significance.
    Graphpad 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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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 10.1101/2021.05.05.442760v1 on bioRxiv