Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures

  1. Jacob D. Galson
  2. Sebastian Schaetzle
  3. Rachael J. M. Bashford-Rogers
  4. Matthew I. J. Raybould
  5. Aleksandr Kovaltsuk
  6. Gavin J. Kilpatrick
  7. Ralph Minter
  8. Donna K. Finch
  9. Jorge Dias
  10. Louisa K. James
  11. Gavin Thomas
  12. Wing-Yiu Jason Lee
  13. Jason Betley
  14. Olivia Cavlan
  15. Alex Leech
  16. Charlotte M. Deane
  17. Joan Seoane
  18. Carlos Caldas
  19. Daniel J. Pennington
  20. Paul Pfeffer
  21. Jane Osbourn

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Abstract

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses.

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  1. Version published to 10.3389/fimmu.2020.605170
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    SciScore for 10.1101/2020.05.20.106294: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Clinical information gathering: Peripheral blood was obtained from patients admitted with acute COVID-19 pneumonia to medical wards at Barts Health NHS Trust, London, UK, after informed consent by the direct care team (NHS HRA RES Ethics 19/SC/0361).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Public SARS-CoV-2 bronchoalveolar lavage RNAseq data processing: The bronchoalveolar lavage data comes from a previously published study of SARS-CoV-2 infection 23, with data available under the PRJNA605983 BioProject on NCBI.
    BioProject
    suggested: (NCBI BioProject, RRID:SCR_004801)
    Public COVID-19 BCR sequence data processing: The fourteen MiSeq “read 1” FASTQ datasets from the six SARS-CoV-2 patients analysed in Nielsen et al.14 were downloaded from the Sequence Read Archive 39.
    MiSeq
    suggested: (A5-miseq, RRID:SCR_012148)
    Plotting was performed using ggplot2 42
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    Results from OddPub: Thank you for sharing your data.

    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.

    About SciScore

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  3. Version published to 10.1101/2020.05.20.106294v1 on bioRxiv