Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection

  1. Vijendra Ramlall
  2. Phyllis M. Thangaraj
  3. Cem Meydan
  4. Jonathan Foox
  5. Daniel Butler
  6. Jacob Kim
  7. Ben May
  8. Jessica K. De Freitas
  9. Benjamin S. Glicksberg
  10. Christopher E. Mason
  11. Nicholas P. Tatonetti
  12. Sagi D. Shapira

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Abstract

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  1. Version published to 10.1038/s41591-020-1021-2
  2. ScreenIT

    SciScore for 10.1101/2020.05.05.20092452: (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

    Software and Algorithms
    SentencesResources
    Statistical Software: We used Jupyter Notebooks (jupyter-client version 5.3.4 and jupyter-core version 4.6.1) running Python 3.7 and all fit models using the python lifelines package (version 0.24.4).
    Python
    suggested: (IPython, RRID:SCR_001658)
    Briefly, reads were trimmed with TrimGalore, aligned with STAR (v2.6.1d) to the human reference build GRCh38 and the GENCODE v33 transcriptome
    TrimGalore
    suggested: None
    STAR
    suggested: (STAR, RRID:SCR_015899)
    GENCODE
    suggested: (GENCODE, RRID:SCR_014966)
    reference, gene expression was quantified using featureCounts, stringTie and salmon using the nf-core RNAseq pipeline.
    featureCounts
    suggested: (featureCounts, RRID:SCR_012919)
    stringTie
    suggested: (StringTie , RRID:SCR_016323)
    Sample QC was reported using fastqc, RSeQC, qualimap, dupradar, Preseq and MultiQC. Reads, as reported by featureCounts, were normalized using variance- stabilizing transform (vst) in DESeq2 package in R and DESeq2 was used to call differential expression with either Positive cases vs Negative, or viral load (High/Medium/Low/None) as reported by RT-PCR cycle threshold (Ct) values.
    RSeQC
    suggested: (RSeQC, RRID:SCR_005275)
    qualimap
    suggested: (QualiMap, RRID:SCR_001209)
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    Both r and p are fit using non-linear least squares (the curve_fit function in scipy.optimize) on , the count data from the permutation analyses for the given α and d.
    scipy
    suggested: (SciPy, RRID:SCR_008058)
    We used PLINK v1.90b6.10 64-bit (17 Jun 2019) to identify haplotype blocks based on linkage disequilibrium.
    PLINK
    suggested: (PLINK, RRID:SCR_001757)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Moreover, retrospective studies of observational data have notable limitations in their data completeness, selection biases, and methods of data capture. As a result, claims on causality cannot be made - nor can we definitively rule out other clinical factors as possible drivers. Nevertheless, in an orthogonal analysis of 650 transcriptional profiles of NP swabs, we demonstrate that in addition to immune factors like Type I interferons and dysregulation of IL-6-dependent inflammatory responses, SARS-CoV-2 infection results in engagement and robust activation of complement and coagulation cascades. Dysregulation of complement and coagulation pathways leading to pathology resulting from viral infection is not without precedent. Indeed, it has been associated with Dengue virus infection where immune mediated pathology and dysregulation of complement is correlated with disease severity and mirrors that of acute SARS-CoV-2 disease24. Moreover, though different from the variants identified in this study, polymorphisms and haplotypes in CFH have been associated with severity of Dengue infection25, suggesting that complement and coagulatory disfunctions may represent risk factors for a broader range of pathogens. Finally, since complement and coagulative dysfunctions can have both acquired and congenital etiologies, we implemented a focused, candidate-driven analysis of UK Biobank data to evaluate linkage between severe SARS-CoV-2 disease and genetic variation associated with complem...

    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.

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  3. Version published to 10.1101/2020.05.05.20092452 on medRxiv