Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection

  1. Marina Vogel-González
  2. Marc Talló-Parra
  3. Víctor Herrera-Fernández
  4. Gemma Pérez-Vilaró
  5. Miguel Chillón
  6. Xavier Nogués
  7. Silvia Gómez-Zorrilla
  8. Inmaculada López-Montesinos
  9. Isabel Arnau-Barrés
  10. Maria Luisa Sorli-Redó
  11. Juan Pablo Horcajada
  12. Natalia García-Giralt
  13. Julio Pascual
  14. Juana Díez
  15. Rubén Vicente
  16. Robert Güerri-Fernández

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Abstract

Background: Zinc is an essential micronutrient that impacts host–pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. Methods: We ran an observational cohort study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel, we have studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) replication in the Vero E6 cell line modifying zinc concentrations. Findings: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dL at admission correlated with worse clinical presentation, longer time to reach stability, and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV-2 infected cells. Interpretation: Low SZC is a risk factor that determines COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.07.20208645: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The Institutional Ethics Committee of Hospital del Mar of Barcelona approved the study and due to the nature of the retrospective data review, and waived the need for informed consent from individual patients (CEIm 2020/9352).
    Consent: The Institutional Ethics Committee of Hospital del Mar of Barcelona approved the study and due to the nature of the retrospective data review, and waived the need for informed consent from individual patients (CEIm 2020/9352).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Primary antibodies were diluted in blocking solution: LC3 (L8918, Sigma) at 1:500; p62 (ab155686, Abcam) at 1:1000; GAPDH (ab8245, Abcam) at 1:1000; and incubated overnight at 4°C.
    LC3
    suggested: (Sigma-Aldrich Cat# L8918, RRID:AB_1079382)
    p62
    suggested: (Abcam Cat# ab155686, RRID:AB_2847961)
    GAPDH
    suggested: (Abcam Cat# ab8245, RRID:AB_2107448)
    Anti-rabbit or anti-mouse HRP secondary antibodies (1:1000; GE Healthcare) were used.
    Anti-rabbit
    suggested: None
    anti-mouse HRP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus infection and quantification: Vero E6 cells were infected with SARS-CoV-2 strain hCoV-19/Spain/VH000001133/2020 (EPI_ISL_418860) and 48 h later viral RNA from the supernatant was extracted using the Quick-RNA Viral Kit (Zymo Research).
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    When indicated, FBS was incubated according to the manufacturer’s instructions with Chelex 100 resin (Bio-Rad Laboratories) to generate Zn2+-free growth medium.
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Analysis was performed using GraphPad software.
    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 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.

  2. Version published to 10.3390/nu13020562
  3. Version published to 10.1101/2020.10.07.20208645v1 on medRxiv