Novel prognostic determinants of COVID-19-related mortality: A pilot study on severely-ill patients in Russia

  1. Kseniya Rubina
  2. Anna Shmakova
  3. Aslan Shabanov
  4. Yulii Andreev
  5. Natalia Borovkova
  6. Vladimir Kulabukhov
  7. Anatoliy Evseev
  8. Konstantin Popugaev
  9. Sergey Petrikov
  10. Ekaterina Semina

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Abstract

COVID-19 pandemic has posed a severe healthcare challenge calling for an integrated approach in determining the clues for early non-invasive diagnostics of the potentially severe cases and efficient patient stratification. Here we analyze the clinical, laboratory and CT scan characteristics associated with high risk of COVID-19-related death outcome in the cohort of severely-ill patients in Russia. The data obtained reveal that elevated dead lymphocyte counts, decreased early apoptotic lymphocytes, decreased CD14+/HLA-Dr+ monocytes, increased expression of JNK in PBMCs, elevated IL-17 and decreased PAI-1 serum levels are associated with a high risk of COVID-19-related mortality thus suggesting them to be new prognostic factors. This set of determinants could be used as early predictors of potentially severe course of COVID-19 for trials of prevention or timely treatment.

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  1. Version published to 10.1371/journal.pone.0264072
  2. ScreenIT

    SciScore for 10.1101/2021.04.01.21254688: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the ethics committee of Sklifosovsky Research Institute of Emergency Medicine of the Moscow Healthcare Department (protocol #5-120, issued on 01.04.2020).
    Consent: The need for written patient consent was waived by the ethics committee of the hospital because laboratory investigations were conducted according to the local standard.
    IACUC: The local ethical committee approved the retrospective study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibodies against the following surface markers were applied for whole blood sample labelling: CD95 (mouse monoclonal anti-hu CD95-FITC 1F-362-T100, EXBIO), CD14 (mouse monoclonal anti-hu CD14-PE Conjugated Antibody A07764, Beckman Coulter) and HLA-Dr (HLA-Dr-FITC Conjugated Antibody, IM1638U, Beckman Coulter).
    CD95
    suggested: (EXBIO Praha Cat# 1F-362-T100, RRID:AB_10735518)
    anti-hu CD95-FITC
    suggested: None
    CD14
    suggested: (Miltenyi Biotec Cat# 130-098-067, RRID:AB_2660171)
    anti-hu CD14-PE
    suggested: None
    HLA-Dr
    suggested: (Beckman Coulter Cat# IM1638U, RRID:AB_10639293)
    For lymphocyte death analysis, PBMCs were stained with anti-CD45, Annexin V, 7AAD (mouse monoclonal anti-hu CD45-FITC Conjugated Antibody A07782 Beckman Coulter; Annexin V-FITC Kit-AAD Kit, IM3614, Beckman Coulter; 7-AAD Viability Dye A07704, Beckman Coulter).
    anti-CD45
    suggested: None
    Annexin V, 7AAD (mouse monoclonal anti-hu CD45-FITC
    suggested: None
    anti-hu
    suggested: None
    Software and Algorithms
    SentencesResources
    In all cases, semi-quantitative CT scoring (severity ranging from 0 to 4) was evaluated according to the protocol recommended by Moscow Healthcare Department adapted from the International Protocols and enriched with local experience 8.
    Moscow Healthcare
    suggested: None

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.04.01.21254688 on medRxiv