The Potential of Low Molecular Weight Heparin to Mitigate Cytokine Storm in Severe COVID‐19 Patients: A Retrospective Cohort Study

  1. Chen Shi
  2. Cong Wang
  3. Hanxiang Wang
  4. Chao Yang
  5. Fei Cai
  6. Fang Zeng
  7. Fang Cheng
  8. Yihui Liu
  9. Taotao Zhou
  10. Bin Deng
  11. Israel Vlodavsky
  12. Jin‐Ping Li
  13. Yu Zhang

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Abstract

On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID‐19) as a global pandemic. However, specific anti‐severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID‐19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group ( P  = 0.011). Likewise, changes in the levels of D‐dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group ( P  = 0.035). Remarkably, IL‐6 levels were significantly reduced after LMWH treatment ( P  = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti‐inflammatory effect and attenuate in part the “cytokine storm” induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID‐19, paving the way for a subsequent well‐controlled clinical study.

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  1. Version published to 10.1111/cts.12880
  2. ScreenIT

    SciScore for 10.1101/2020.03.28.20046144: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the institutional review board of the hospital.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: Data analysis was performed using SPSS 22·0 statistical software.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    GraphPad 6·0 software was used for plotting.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Limitations: This study has several limitations. First, due to the retrospective design, we were unable to control the time intervals between examinations of the various indices in patients and the LMWH treatment schedule. Likewise, we could not estimate and manage the effective dose and timing of LMWH. Second, there were no critical cases in the two groups of patients; the treatment outcome of all cases was improvement and discharge, and there were no deaths. Finally, the findings are limited by the sample size and single-center design of our study.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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 10.1101/2020.03.28.20046144v3 on medRxiv
  4. Version published to 10.1101/2020.03.28.20046144v2 on medRxiv
  5. Version published to 10.1101/2020.03.28.20046144v1 on medRxiv