COVID-19 patients have increased levels of membrane-associated and soluble CD48

  1. Hadas Pahima
  2. Ilan Zaffran
  3. Eli Ben-Chetrit
  4. Amir Jarjoui
  5. Pratibha Gaur
  6. Maria Laura Manca
  7. Dana Reichmann
  8. Efrat Orenbuch-Harroch
  9. Ilaria Puxeddu
  10. Carl Zinner
  11. Alexandar Tzankov
  12. Francesca Levi-Schaffer

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Abstract

COVID-19 is a respiratory-centered systemic disorder caused by SARS-CoV-2. The disease can progress into a severe form causing acute lung injury.

CD48 is a co-signaling receptor, existing as both membrane-bound and soluble forms reported to be dysregulated in several inflammatory conditions. Therefore, we reasoned that CD48 could be deregulated in COVID-19 as well.

Here we analyzed CD48 expression in autoptic sections and peripheral blood leukocytes and sera of COVID-19 patients by gene expression profiling (HTG® autoimmune panel), immunohistochemistry, flow cytometry and ELISA.

Lung tissue of COVID-19 patients showed increased CD48 mRNA expression and infiltration of CD48+ lymphocytes. In the peripheral blood, mCD48 was considerably increased on all evaluated cells, and additionally, sCD48 levels were significantly higher in COVID-19 patients independently of disease severity. Considering the alterations of mCD48 and sCD48, a specific role for CD48 in COVID-19 can be assumed, suggesting it as a potential target for therapy.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.18.484843: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Tissue collection was approved by the Ethics committee of Northern and Central Switzerland (study ID 2020-00969).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    anti-CD48 antibody (EPR4108; ab134049; Abcam, Cambridge, UK), washed, and counterstained with hematoxylin (Gill II).
    anti-CD48
    suggested: None
    Software and Algorithms
    SentencesResources
    Gene Expression Programming (GEP) of lung tissue: GEP of the lung tissue obtained at autopsy and used for the TMA construction was performed by HTG according to established protocols (https://www.htgmolecular.com/assets/htg/resources/BR-05-HTG-EdgeSeq-System.pdf).
    Gene Expression Programming
    suggested: None
    A PCA analysis was then performed using the pcomp function in R©, version 4.0.3 (R-Project for Statistical Computing, Vienna, Austria) and differential expression analysis of COVID-19 cases against controls was conducted with the DESeq2 package using default settings.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    The heatmap was produced with the pheatmap package.
    pheatmap
    suggested: (pheatmap, RRID:SCR_016418)
    Thereafter, cells were washed twice (250g, 5 min, 4°C) with 0.1% BSA/PBS, and FC data were acquired by BD LSR II Flow Cytometer and analyzed with FlowJo software (Tree Star, OR, USA)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Data were analyzed by Prism version 9.0 (GraphPad Software, San Diego, California, USA).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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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  2. Version published to 10.1101/2022.03.18.484843v1 on bioRxiv