Class I HLA Allele Predicted Restricted Antigenic Coverages for Spike and Nucleocapsid Proteins Are Associated With Deaths Related to COVID-19

  1. Marco Antônio M. Pretti
  2. Rômulo G. Galvani
  3. Gustavo Fioravanti Vieira
  4. Adriana Bonomo
  5. Martín H. Bonamino
  6. Mariana Boroni

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Abstract

The world is dealing with one of the worst pandemics ever. SARS-CoV-2 is the etiological agent of COVID-19 that has already spread to more than 200 countries. However, infectivity, severity, and mortality rates do not affect all countries equally. Here we consider 140 HLA alleles and extensively investigate the landscape of 3,723 potential HLA-I A and B restricted SARS-CoV-2-derived antigens and how 37 countries in the world are predicted to respond to those peptides considering their HLA-I distribution frequencies. The clustering of HLA-A and HLA-B allele frequencies partially separates most countries with the lowest number of deaths per million inhabitants from the other countries. We further correlated the patterns of in silico predicted population coverage and epidemiological data. The number of deaths per million inhabitants correlates to the predicted antigen coverage of S and N derived peptides and its module is influenced if a given set of frequent or rare HLA alleles are analyzed in a given population. Moreover, we highlighted a potential risk group carrying HLAs associated with an elevated number of deaths per million inhabitants. In addition, we identified three potential antigens bearing at least one amino acid of the four-length insertion that differentiates SARS-CoV-2 from previous coronavirus strains. We believe these data can contribute to the search for peptides with the potential to be used in vaccine strategies considering the role of herd immunity to hamper the spread of the disease. Importantly, to the best of our knowledge, this work is the first to use a populational approach in association with COVID-19 outcome.

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  1. Version published to 10.3389/fimmu.2020.565730
  2. Version published to 10.1101/2020.06.03.20121301v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.06.03.20121301: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Allele frequencies with resolution greater than two fields were combined, e.g. for BRA: B*07:02:01 and B*07:02:03 became B*07:02.
    B*07:02:01
    suggested: None
    Software and Algorithms
    SentencesResources
    We used blastp v2.9.0 to eliminate peptides that matched protein sequences from the Ensembl human genome GRCh38 with 100% of identity and same query length.
    blastp
    suggested: (BLASTP, RRID:SCR_001010)
    Ensembl
    suggested: (Ensembl, RRID:SCR_002344)
    Data analysis: The analysis was conducted using the R environment version 4.0 and the following packages ggpubr v0.2.1, ggplot2 v3.2.1, data.table v1.12.2, gridExtra v2.3, readxl v1.3.1, dplyr v0.8.3, tidytext v0.2.3, pheatmap v1.0.12, RColorBrewer v1.1, cowplot v1.0, GenomicRanges v1.31.1, IRanges v2.18.1, stats v4.0.2, boot v1.3, ggfortify v0.10 and ggbio v1.32.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    pheatmap
    suggested: (pheatmap, RRID:SCR_016418)
    RColorBrewer
    suggested: (RColorBrewer, RRID:SCR_016697)
    cowplot
    suggested: (cowplot, RRID:SCR_018081)
    GenomicRanges
    suggested: (GenomicRanges, RRID:SCR_000025)
    IRanges
    suggested: (IRanges, RRID:SCR_006420)

    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

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  4. Version published to 10.1101/2020.06.03.20121301v1 on medRxiv