Excessive Matrix Metalloproteinase-1 and Hyperactivation of Endothelial Cells Occurred in COVID-19 Patients and Were Associated With the Severity of COVID-19

  1. Fahim Syed
  2. Wei Li
  3. Ryan F Relich
  4. Patrick M Russell
  5. Shanxiang Zhang
  6. Michelle K Zimmerman
  7. Qigui Yu

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Systemic vascular injury occurs in coronavirus disease 2019 (COVID-19) patients; however, the underlying mechanisms remain unknown.

Methods

To clarify the role of inflammatory factors in COVID-19 vascular injury, we used a multiplex immunoassay to profile 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs).

Results

COVID-19 patients had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only 1 cytokine, macrophage migration inhibitory factor (MIF), was among these altered analytes, while the rest were chemokines/growth factors. Additionally, only matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. We further studied MMP-1 enzymatic activity and multiple endothelial cell (EC) activation markers (soluble forms of CD146, intercellular adhesion molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) and found that they were highly dysregulated in COVID-19 patients.

Conclusions

COVID-19 patients have a unique inflammatory profile, and excessive MMP-1 and hyperactivation of ECs are associated with the severity of COVID-19.

Article activity feed

  1. Version published to 10.1093/infdis/jiab167
  2. ScreenIT

    SciScore for 10.1101/2021.01.19.21250115: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study subjects and ethical considerations: This study was performed with the approval of the Institutional Review Boards at Indiana University School of Medicine.
    Consent: Blood samples were drawn after each participant provided a written informed consent form.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Briefly, diluted plasma samples and MMP-1 standards were added to the wells that were pre-coated with a monoclonal antibody specific for human MMP-1.
    MMP-1
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Plasma concentrations of 65 human cytokines/chemokines/growth factors including 33 cytokines (G-CSF, GM-CSF, IFN-α, IFN-γ, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-18, IL-20, IL-21, IL-22, IL-23, IL-27, IL-31, LIF, M-CSF, MIF, TNF-α, TNF-β, and TSLP), 18 chemokines (CXCL13, CXCL5, CCL11, CCL24, CCL26, CX3CL1, CXCL1, CXCL10, CXCL11, MCP-1, MCP-2, MCP-3, MDC, MIG, MIP-1α, MIP-1β, MIP-3α, and SDF-1α), 6 growth factors/regulators (FGF-2, HGF, MMP-1, NGF-β, SCF, VEGF-A), and 8 soluble receptors (APRIL, BAFF, CD30, CD40L, IL-2R, TNF-RII, TRAIL, and TWEAK) were simultaneously measured using a magnetic bead-based multiplex kit (65-Plex Human ProcartaPlex™ Panel, EPX650-10065-901
    MCP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    After washing twice, beads were resuspended in PBS and read on a BioPlex 200 system (Bio-Rad, Hercules, CA) with a setting of 40 beads per bead set and 150 seconds per well.
    BioPlex
    suggested: (BioPlex, RRID:SCR_016144)
    Statistical analysis: Statistical analysis was performed using GraphPad Prism 6.0 (La Jolla, CA).
    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: 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 10.1101/2021.01.19.21250115v1 on medRxiv