Proteomic blood profiling in mild, severe and critical COVID-19 patients

  1. Hamel Patel
  2. Nicholas J. Ashton
  3. Richard J. B. Dobson
  4. Lars-Magnus Andersson
  5. Aylin Yilmaz
  6. Kaj Blennow
  7. Magnus Gisslen
  8. Henrik Zetterberg

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Abstract

The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.

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  1. Version published to 10.1038/s41598-021-85877-0
  2. ScreenIT

    SciScore for 10.1101/2020.06.22.20137216: (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

    Software and Algorithms
    SentencesResources
    Additional data processing was performed in RStudio (version 1.2.1335) using R (version 3.6.0).
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    The two longitudinal analyses were performed in their respective disease groups using a paired t-test approach in limma.
    limma
    suggested: (LIMMA, RRID:SCR_010943)
    Pathway enrichment analysis was performed using an Over-Representation Analysis (ORA) implemented through the ConsensusPathDB (http://cpdb.molgen.mpg.de) web-based platform (version 34) (38).
    ConsensusPathDB
    suggested: (ConsensusPathDB, RRID:SCR_002231)

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

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Due to blood samples being taken as part of a routine hospital procedure during an unprecedented time, this study was restricted to a small cohort, certain aspects of this study design were uncontrollable and valuable information was unobtainable. The number of “days since symptom onset”, was identified to be significantly higher in the mild symptom group when compared to the severe and the critical symptom group. Essentially, following the onset of symptoms, samples were drawn from the mild symptom group at a much later date when compared to the severe and the critical symptom group. As a result, expression changes involving the mild group (“mild vs severe” and “mild vs critical”) may reflect the duration a patient has been infected with COVID-19 rather than being a reflection of symptom severity. However, as the longitudinal analysis in this study measures protein expression changes during infection, these results were used to differentiate between expression changes likely due to disease severity and duration of infection. Furthermore, information on comorbidities, medical history and medications are unknown. Hospitalized patients with COVID-19 are known to be more likely to have an underlying health disorder such as hypertension, obesity and diabetes (35), and it is unknown if this cohort has the same characteristics. Moreover, it is unknown if any medication, in addition to oxygen supplementation, was administered to COVID-19 patients, therefore; protein exp...

    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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  3. Version published to 10.1101/2020.06.22.20137216v1 on medRxiv