Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module

  1. Hye Kyung Lee
  2. Ludwig Knabl
  3. Ludwig Knabl
  4. Manuel Wieser
  5. Anna Mur
  6. August Zabernigg
  7. Jana Schumacher
  8. Sebastian Kapferer
  9. Norbert Kaiser
  10. Priscilla A. Furth
  11. Lothar Hennighausen

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Abstract

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in BCs from hospitalized patients infected with either the Alpha variant (n = 36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n = 13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Beta (n = 9) and Gamma (n = 3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.

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  1. Version published to 10.1038/s41598-022-06752-0
  2. ScreenIT

    SciScore for 10.1101/2021.05.27.21257952: (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

    Software and Algorithms
    SentencesResources
    The raw data were subjected to QC analyses using the FastQC tool (version 0.11.9) (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/).
    FastQC
    suggested: (FastQC, RRID:SCR_014583)
    mRNA-seq read quality control was done using Trimmomatic15 (version 0.36) and STAR RNA-seq16 (version STAR 2.5.4a) using 150 bp paired-end mode was used to align the reads (hg19).
    STAR
    suggested: (STAR, RRID:SCR_004463)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: The findings in this report are subject to several limitations. Our study focused on hospitalized patients in a specific geographic area. Our study focused on elderly patients with limited comparison to younger individuals. We have investigated the effect of the BNT162b vaccine but not of any other vaccine.

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.05.27.21257952v1 on medRxiv