Transcriptome Analysis of Peripheral Blood Mononuclear Cells Reveals Distinct Immune Response in Asymptomatic and Re-Detectable Positive COVID-19 Patients

  1. Jiaqi Zhang
  2. Dongzi Lin
  3. Kui Li
  4. Xiangming Ding
  5. Lin Li
  6. Yuntao Liu
  7. Dongdong Liu
  8. Jing Lin
  9. Xiangyun Teng
  10. Yizhe Li
  11. Ming Liu
  12. Jian Shen
  13. Xiaodan Wang
  14. Dan He
  15. Yaling Shi
  16. Dawei Wang
  17. Jianhua Xu

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Abstract

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.

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  1. Version published to 10.3389/fimmu.2021.716075
  2. ScreenIT

    SciScore for 10.1101/2021.03.16.21251286: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Patients: This study was reviewed and approved by the ethics committees of the above four participant hospitals.
    Consent: Written informed consent was obtained from all participants enrolled in this
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data processing and analysis: Cutadapt software (cutadapt v1.16) was used to remove the reads contained adaptor contamination.
    Cutadapt
    suggested: (cutadapt, RRID:SCR_011841)
    The clean reads were mapped to the hg19 UCSC transcript set using Bowtie2 version 2.1.0 and the gene expression level was estimated using RSEM v1.2.15.
    Bowtie2
    suggested: (Bowtie 2, RRID:SCR_016368)
    RSEM
    suggested: (RSEM, RRID:SCR_013027)

    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: We detected the following sentences addressing limitations in the study:
    Several limitations should be taken into consideration for the interpretation of this study. First, this study focused on the transcriptome analysis of PBMCs in blood. Adding the data of immune cells from lesion sites such as the lung and bronchoalveolar lavage fluid will make the analysis more comprehensive and conclusive. Second, the PBMC samples were collected within 4 days of admission from asymptomatic and symptomatic groups to maintain uniformity of timing for comparison between groups. Future studies with longitudinal samples from COVID-19 patients may help to determine the cause-and-effect relationships between immune response and disease outcome. In summary, this study will help us extend our understanding of host immune response during the progression COVID-19 disease, and may help elucidate the COVID-19 infection and provide a basis for rationally designed immune therapies.

    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 10.1101/2021.03.16.21251286 on medRxiv