Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients

  1. Eduardo Cervantes-Alvarez
  2. Nathaly Limon-de la Rosa
  3. Moises Salgado-de la Mora
  4. Paola Valdez-Sandoval
  5. Mildred Palacios-Jimenez
  6. Fatima Rodriguez-Alvarez
  7. Brenda I. Vera-Maldonado
  8. Eduardo Aguirre-Aguilar
  9. Juan Manuel Escobar-Valderrama
  10. Jorge Alanis-Mendizabal
  11. Osvely Méndez-Guerrero
  12. Farid Tejeda-Dominguez
  13. Jiram Torres-Ruíz
  14. Diana Gómez-Martín
  15. Kathryn L. Colborn
  16. David Kershenobich
  17. Christene A. Huang
  18. Nalu Navarro-Alvarez

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Abstract

Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47–9.20), p  < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79–0.91, p  < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.

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  1. Version published to 10.1038/s41598-022-05968-4
  2. ScreenIT

    SciScore for 10.1101/2021.02.07.21251281: (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 INCMNSZ’s Research Ethics Committee (No. GAS-3385-20-20-1) and complied with the provisions of the Declaration of Helsinki.
    Consent: Informed written consent was obtained from all patients prior to blood sample collection.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed with SPSS (version 24.0, SPSS Inc., Chicago, IL, USA) and GraphPad Prism (version 8.00, GraphPad Software, La Jolla, CA, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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:
    There are some limitations to our study. First, since this is a single-center experience, data from different populations and a multicenter analysis will be needed for validation. Second, due to the small sample size, further clinical studies with larger sample sizes are required to confirm these findings before galectin-3 can definitively be recommended as a standard biomarker in the hospital setting. Despite these limitations, this study demonstrates in a prospective cohort of COVID-19 patients at one of the largest health institutes in Mexico that measurement of galectin-3 levels upon hospital admission could be helpful in predicting disease severity. Finally, the combined use of galectin-3, CRP and albumin showed strong predictive ability, and thus could aid to efficiently allocate medical resources before patients develop an adverse outcome.

    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 10.1101/2021.02.07.21251281v1 on medRxiv