A multiplex protein panel assay for severity prediction and outcome prognosis in patients with COVID-19: An observational multi-cohort study

  1. Ziyue Wang
  2. Adam Cryar
  3. Oliver Lemke
  4. Pinkus Tober-Lau
  5. Daniela Ludwig
  6. Elisa Theresa Helbig
  7. Stefan Hippenstiel
  8. Leif-Erik Sander
  9. Daniel Blake
  10. Catherine S. Lane
  11. Rebekah L. Sayers
  12. Christoph Mueller
  13. Johannes Zeiser
  14. StJohn Townsend
  15. Vadim Demichev
  16. Michael Mülleder
  17. Florian Kurth
  18. Ernestas Sirka
  19. Johannes Hartl
  20. Markus Ralser

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Abstract

No abstract available

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  1. Version published to 10.1016/j.eclinm.2022.101495
  2. ScreenIT

    SciScore for 10.1101/2021.12.03.21267253: (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: Cell Lines
    SentencesResources
    Quality control (QC) samples consisted of pooled commercial control and COVID-19 human plasma samples (as described in a previous publication [25]), and were prepared alongside clinical and calibration curve samples in each cohort.
    COVID-19
    suggested: None
    Software and Algorithms
    SentencesResources
    (Eluent additive for LC-MS; Cat# 40867) and Dimethyl sulfoxide (DMSO; Cat# 41648) were from Fluka, formic acid (LC-MS Grade; Eluent additive for LC-MS; Cat# 85178) was from Thermo Scientific™,
    Thermo Scientific™
    suggested: (Thermo Scientific Wellwash Wellwash, RRID:SCR_020569)
    The 6495C mass spectrometer was controlled by Agilent’s MassHunter Workstation software (LC-MS/MS Data Acquisition for 6400 series Triple Quadrupole, Version 10.1) and was operated in positive electrospray ionisation mode with the following parameters: 3500 V capillary voltage (positive), 0 V nozzle voltage (positive), 12 L/min sheath gas flow at a temperature of 280°C, 17 L/min gas flow at a temperature of 170°C, 40 psi nebulizer pressure, 166 V fragmentor voltage, 5 V cell accelerator potential.
    Agilent’s MassHunter
    suggested: None
    Mass spectrometry data processing: Mass spectrometry data processing was performed with vendor-specific software: Agilent MassHunter Quantitative Analysis, v10.1 and SCIEX OS Software v2.0.1.
    Agilent MassHunter Quantitative Analysis
    suggested: (Agilent Masshunter Quantitative Analysis software, RRID:SCR_015040)
    Prediction of WHO grade and disease outcome: For the prediction of the current WHO grade and for the outcome prediction a Support Vector Machine was used as implemented in scikit-learn 0.23.2 (sklearn.svm.SVC) [53] using default parameters (rbf-kernel) and balanced class weights (class_weight = ”balanced”).
    scikit-learn
    suggested: (scikit-learn, RRID:SCR_002577)

    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:
    In our study, we overcame a common limitation of proteomic assays for their routine use - their dependency on low flow rate-chromatography [48–50]. Exploiting the high sensitivity of contemporary triple-quadrupole mass spectrometers, we demonstrate the accurate quantification of the peptide panel using analytical flow rate chromatography, which not only is robust and fast, but also routinely used in clinical laboratories for small molecule analysis, greatly simplifying the application of our assay in the clinical routine. The developed biomarker panel includes 50 peptides derived from 30 plasma proteins. The proteins are related to biological processes which have been shown to be important for the COVID-19 host response and pathophysiology, like the innate immune response, the coagulation system or the complement cascade [14,25,26,35]. The assay is hence monitoring processes that are closely linked to disease progression and the exceptionally diverse clinical presentation of patients with SARS-CoV-2 infection. In this study, we established the assay on two routine-laboratory-compatible LC-MRM platforms, and performed analytical validation of the key technical aspects of the assay. We demonstrate excellent sensitivity, accuracy, precision, as well as reproducibility across two different targeted mass spectrometry platforms. Of note, reagents for sample preparation and LC-MRM method setup are also commercially available in standardised kit formats. As such, the assay could be e...

    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 10.1101/2021.12.03.21267253 on medRxiv