Soluble P2X7 receptor is elevated in the plasma of COVID-19 patients and correlates with disease severity

  1. Julio García-Villalba
  2. Laura Hurtado-Navarro
  3. Alejandro Peñín-Franch
  4. Cristina Molina-López
  5. Laura Martínez-Alarcón
  6. Diego Angosto-Bazarra
  7. Alberto Baroja-Mazo
  8. Pablo Pelegrín

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Abstract

Inflammation is a tightly coordinated response against bacterial and viral infections, triggered by the production of pro-inflammatory cytokines. SARS-CoV-2 infection induces COVID-19 disease, characterized by an inflammatory response mediated through the activation of the NLRP3 inflammasome, which results in the production of IL-1β and IL-18 along with pyroptotic cell death. The NLRP3 inflammasome could be also triggered by sterile danger signals such as extracellular ATP triggering the purinergic P2X7 receptor. Severe inflammation in the lungs of SARS-CoV-2 infected individuals is associated with pneumonia, hypoxia and acute respiratory distress syndrome, these being the causes of death associated with COVID-19. Both the P2X7 receptor and NLRP3 have been considered as potential pharmacological targets for treating inflammation in COVID-19. However, there is no experimental evidence of the involvement of the P2X7 receptor during COVID-19 disease. In the present study we determined the concentration of different cytokines and the P2X7 receptor in the plasma of COVID-19 patients and found that along with the increase in IL-6, IL-18 and the IL-1 receptor antagonist in the plasma of COVID-19 patients, there was also an increase in the purinergic P2X7 receptor. Increase in COVID-19 severity and C-reactive protein concentration positively correlated with increased concentration of the P2X7 receptor in the plasma, but not with IL-18 cytokine. The P2X7 receptor was found in the supernatant of human peripheral blood mononuclear cells after inflammasome activation. Therefore, our data suggest that determining levels of the P2X7 receptor in the plasma could be a novel biomarker of COVID-19 severity.

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  1. Version published to 10.1101/2022.03.04.483019v3 on bioRxiv
  2. Version published to 10.1101/2022.03.04.483019v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.03.04.483019: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Human samples: Samples and data from patients included in this study, who gave written informed consent, were collected, processed and provided by the Biobanco en Red de la Región de Murcia, BIOBANC-MUR, registered on the Registro Nacional de Biobancos with registration number B.0000859, and were processed following standard operating procedures with appropriate approval of the Ethical Committees (2021-5-10-HCUVA).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Multiplex: Multiplexing in human serum for IL-15, IL-18, MCP-1, IL-2, IL-6 and IL-1RA was performed using the Luminex color-coded antibody-immobilized beads from Merck Millipore following the manufacture’s indications, and the results were analysed in a Luminex MAGPIX instrument (Luminex Corporation).
    IL-15
    suggested: (Meso Scale Discovery Cat# K15067L, RRID:AB_2905470)
    MCP-1
    suggested: (BioLegend Cat# 741091, RRID:AB_2895549)
    IL-2
    suggested: (BioLegend Cat# 741091, RRID:AB_2895549)
    IL-6
    suggested: (BioLegend Cat# 741091, RRID:AB_2895549)
    Software and Algorithms
    SentencesResources
    Statistics and data analysis: Statistical analyses were performed using GraphPad Prism 9 (GraphPad Software Inc.)
    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2022.03.04.483019v1 on bioRxiv