Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

  1. Haitao Xiang
  2. Yingze Zhao
  3. Xinyang Li
  4. Peipei Liu
  5. Longlong Wang
  6. Meiniang Wang
  7. Lei Tian
  8. Haixi Sun
  9. Wei Zhang
  10. Ziqian Xu
  11. Beiwei Ye
  12. Xiaoju Yuan
  13. Pengyan Wang
  14. Ning Zhang
  15. Yuhuan Gong
  16. Chengrong Bian
  17. Zhaohai Wang
  18. Linxiang Yu
  19. Jin Yan
  20. Fanping Meng
  21. Changqing Bai
  22. Xiaoshan Wang
  23. Xiaopan Liu
  24. Kai Gao
  25. Liang Wu
  26. Longqi Liu
  27. Ying Gu
  28. Yuhai Bi
  29. Yi Shi
  30. Shaogeng Zhang
  31. Chen Zhu
  32. Xun Xu
  33. Guizhen Wu
  34. George F. Gao
  35. Naibo Yang
  36. William J. Liu
  37. Penghui Yang

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient’s immunological status, and found dramatic changes in the IGH within the patients’ immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones during 2-3 weeks of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34 and IGHV4-39 in COVID-19 patients were more abundant than that of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.28.424622: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study approval and samples: This study has been approved by the Research Ethics Committee of The Fifth Medical Center of PLA General Hospital, Beijing, China. (approval number: 2020034D), written informed consent was regularly obtained from all patients.
    Consent: Study approval and samples: This study has been approved by the Research Ethics Committee of The Fifth Medical Center of PLA General Hospital, Beijing, China. (approval number: 2020034D), written informed consent was regularly obtained from all patients.
    RandomizationSecondly, normalized data with the same size were extracted randomly from each sample by an in-house Perl program.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Briefly, the raw reads were filtered and trimmed by SOAPnuke [10] to remove low-quality reads and adapter sequences.
    SOAPnuke
    suggested: (SOAPnuke, RRID:SCR_015025)
    BLAST [12] program was used to align all clean reads to a reference, and then a second alignment procedure was executed to improve the alignment accuracy.
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)
    According to this definition, we first grouped sequence with identical V and J germline gene origination and same CDR3 length, following clustering those group by CD-HIT (version 4.6) [13] with the following parameters: -c 0.9, -G 1, -b 20, -d 0 and -n 9.
    CD-HIT
    suggested: (CD-HIT, RRID:SCR_007105)

    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

    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 10.1101/2020.12.28.424622 on bioRxiv