B cell receptor repertoire analysis unveils dynamic antibody response and severity markers in COVID-19 patients

  1. Soumya Rao
  2. Kriti Srivastava
  3. Anupriya Verma
  4. Achintya Das

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Abstract

Humoral and cell mediated immunity are critical against viral infections. The knowledge of composition, diversity, gene usage of the B cell repertoires helps in determining the immune response to SARS-CoV-2 infection. Examining B cell response provides insights on therapeutic antibodies, disease severity markers and aids in predicting vaccine response. We have analyzed public domain immunoglobulin sequencing data from PBMCs of SARS-CoV-2 infected individuals to gain a better understanding of B cell repertoire in patients. Public clonotypes showed increased usage of IGHV3, IGHV4, IGKV1, IGKV3, IGLV3 and IGLV2 family genes during the acute phase infection. Identical CDR3 sequences were identified for heavy (H), kappa (K) and lambda (L) chains across individuals, indicating the convergence of B cell selection during SARS-CoV-2 infection. While the immune repertoire dynamically changed over the course of convalescence, there were persistent clones across early and late timepoints. The diversity of antibody repertoire, measured by Shannon-Weiner diversity index for H and K chains, reduced during the acute phase of infection. In addition, the repertoire diversity was low in severe patients compared to patients with mild or moderate symptoms. Increased usage of IGHV4-59 gene was observed in COVID-19 patients with severe symptoms requiring ventilator support at 2 weeks and 3 weeks post symptom onset. IGHV4-59 is reported to have rheumatoid factor (RF) activity with high affinity for IgG and the elevated level of IGHV4-59 provides a potential mechanism for the increased autoimmune responses in severe patients. Correlation of the clinical features with the B cell receptor repertoire dynamics elucidated public antibody clonotypes and disease severity markers for COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.24.485649: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    The R1 and R2 were then assembled using pRESTO, The Repertoire Sequencing Toolkit (15).
    pRESTO
    suggested: None
    Software and Algorithms
    SentencesResources
    FastQC was performed on read 1 (R1) and read 2 (R2) separately.
    FastQC
    suggested: (FastQC, RRID:SCR_014583)
    The assembled reads were subjected to trimming using quality Phred score 20 as cutoff.
    Phred
    suggested: (Phred, RRID:SCR_001017)
    The quality trimmed reads were further processed using IgBLAST (17).
    IgBLAST
    suggested: (IgBLAST, RRID:SCR_002873)
    R package circlize (20) was used to create chord diagram for visualizing V-J usage frequencies.
    circlize
    suggested: (circlize, RRID:SCR_002141)
    To assess the closeness of the repertoire across samples, Jaccard distance was calculated using vegan package.
    vegan
    suggested: (vegan, RRID:SCR_011950)

    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.
    • No funding statement was detected.
    • 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 10.1101/2022.03.24.485649v1 on bioRxiv