Single-Cell Immunogenomic Approach Identified SARS-CoV-2 Protective Immune Signatures in Asymptomatic Direct Contacts of COVID-19 Cases

  1. Kaushik Sen
  2. Sudeshna Datta
  3. Arup Ghosh
  4. Atimukta Jha
  5. Abdul Ahad
  6. Sanchari Chatterjee
  7. Sandhya Suranjika
  8. Soumya Sengupta
  9. Gargee Bhattacharya
  10. Omprakash Shriwas
  11. Kiran Avula
  12. Jayasingh Kshatri
  13. Punit Prasad
  14. Rajeeb Swain
  15. Ajay K. Parida
  16. Sunil K. Raghav

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Abstract

The response to severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2) is largely impacted by the level of virus exposure and status of the host immunity. The nature of protection shown by direct asymptomatic contacts of coronavirus disease 2019 (COVID-19)-positive patients is quite intriguing. In this study, we have characterized the antibody titer, SARS-CoV-2 surrogate virus neutralization, cytokine levels, single-cell T-cell receptor (TCR), and B-cell receptor (BCR) profiling in asymptomatic direct contacts, infected cases, and controls. We observed significant increase in antibodies with neutralizing amplitude in asymptomatic contacts along with cytokines such as Eotaxin, granulocyte-colony stimulating factor (G-CSF), interleukin 7 (IL-7), migration inhibitory factor (MIF), and macrophage inflammatory protein-1α (MIP-1α). Upon single-cell RNA (scRNA) sequencing, we explored the dynamics of the adaptive immune response in few representative asymptomatic close contacts and COVID-19-infected patients. We reported direct asymptomatic contacts to have decreased CD4 + naive T cells with concomitant increase in CD4 + memory and CD8 + Temra cells along with expanded clonotypes compared to infected patients. Noticeable proportions of class switched memory B cells were also observed in them. Overall, these findings gave an insight into the nature of protection in asymptomatic contacts.

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  1. Version published to 10.3389/fimmu.2021.733539
  2. ScreenIT

    SciScore for 10.1101/2021.03.11.21253367: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Secondary antibody HRP Goat anti-human IgA (Biolegend #411002) and GtX Hu IgM HRP (Merck Millipore # Lot: 3462097) were used at a dilution of 1:2500 for 1h at 37□ for IgA and IgM quantification respectively.
    anti-human IgA
    suggested: (BioLegend Cat# 411002, RRID:AB_2686938)
    For quantification of total COVID-19 and IgG antibodies, kits namely COVID-19 (IgG + Ig M + Ig A) Microlisa and Covid Kawach IgG Microlisa (# IR200196) were used (J. mitra & Co.) respectively.
    IgG
    suggested: None
    After blocking, cells were washed with 1x FACS buffer and incubated with conjugated primary antibodies anti-human CD19 PB (eBiosciences # 48-0199-42).
    anti-human CD19
    suggested: (BioLegend Cat# 392505, RRID:AB_2750096)
    Cells from individual patient samples were incubated with anti-human TotalSeq™-C antibodies (C0251 BioLegend # 394661, C0252 BioLegend # 394663 and C0253 BioLegend # 394665), washed and treated with PI viability dye (BioLegend #79997).
    anti-human TotalSeq™-C
    suggested: None
    C0253
    suggested: (Assay Biotech Cat# C0253, RRID:AB_10684577)
    Software and Algorithms
    SentencesResources
    After identification of the CDR3 sequences and the rearranged BCR genes, analysis was performed using Loupe V(D)J Browser v.2.0.1.
    Loupe V(D)J Browser
    suggested: None
    The pie chart of antibodies was created using the GGPLOT2 package and all the respective p-values in box plots are calculated using Wilcoxon test and stat_compare_means (paired = FALSE) function for respective condition pairs.
    GGPLOT2
    suggested: (ggplot2, RRID:SCR_014601)

    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.

    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.

  3. Version published to 10.1101/2021.03.11.21253367v1 on medRxiv