Alcohol Consumption Is Associated with Poor Prognosis in Obese Patients with COVID-19: A Mendelian Randomization Study Using UK Biobank

  1. Xiude Fan
  2. Zhengwen Liu
  3. Kyle L. Poulsen
  4. Xiaoqin Wu
  5. Tatsunori Miyata
  6. Srinivasan Dasarathy
  7. Daniel M. Rotroff
  8. Laura E. Nagy

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Abstract

Background: Acute and chronic alcohol abuse has adverse impacts on both the innate and adaptive immune response, which may result in reduced resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and promote the progression of coronavirus disease 2019 (COVID-19). However, there are no large population-based data evaluating potential causal associations between alcohol consumption and COVID-19. Methods: We conducted a Mendelian randomization study using data from UK Biobank to explore the association between alcohol consumption and risk of SARS-CoV-2 infection and serious clinical outcomes in patients with COVID-19. A total of 12,937 participants aged 50–83 who tested for SARS-CoV-2 between 16 March to 27 July 2020 (12.1% tested positive) were included in the analysis. The exposure factor was alcohol consumption. Main outcomes were SARS-CoV-2 positivity and death in COVID-19 patients. We generated allele scores using three genetic variants (rs1229984 (Alcohol Dehydrogenase 1B, ADH1B), rs1260326 (Glucokinase Regulator, GCKR), and rs13107325 (Solute Carrier Family 39 Member 8, SLC39A8)) and applied the allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. Analyses were conducted separately for white participants with and without obesity. Results: Of the 12,937 participants, 4496 were never or infrequent drinkers and 8441 were frequent drinkers. Both logistic regression and Mendelian randomization analyses found no evidence that alcohol consumption was associated with risk of SARS-CoV-2 infection in participants either with or without obesity (All q > 0.10). However, frequent drinking, especially heavy drinking (HR = 2.07, 95%CI 1.24–3.47; q = 0.054), was associated with higher risk of death in patients with obesity and COVID-19, but not in patients without obesity. Notably, the risk of death in frequent drinkers with obesity increased slightly with the average amount of alcohol consumed weekly (All q < 0.10). Conclusions: Our findings suggest that alcohol consumption has adverse effects on the progression of COVID-19 in white participants with obesity, but was not associated with susceptibility to SARS-CoV-2 infection.

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  1. Version published to 10.3390/nu13051592
  2. ScreenIT

    SciScore for 10.1101/2020.11.25.20238915: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: UK Biobank has obtained Research Tissue Bank (RTB) approval from its ethics committee and this study was also approved by the Institutional Review Boards of the Cleveland Clinic (IRB number:19582).
    Consent: Participants enrolled in UK Biobank have signed consent forms.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Strengths and Limitations: One of main advantages of this study is the application of Mendelian randomization to evaluate the causal relationships between alcohol consumption and the risk of SARS CoV2 infection and the severity of COVID-19 outcomes. To our knowledge, the associations between alcohol and risk of COVID-19 have not been previously explored using Mendelian randomization. We generated weighted and unweighted allele scores using three SNPs rs1229984 (ADH1B), rs1260326 (GCKR), and rs13107325 (SLC39A8) and applied the weighted and unweighted allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. These three SNPs were randomly distributed among the white participants and were not associated with other confounders that may affect outcomes. However, rs1229984, rs1260326, and rs13107325 were significantly correlated with obesity. This issue was well addressed by our separate analysis based on whether the white participants were obese or not. In addition, the Mendelian randomization approach more robustly handles measurement error and reverse causality compared to traditional observational approaches. Another major advantage of our study is the detailed data in a larger population-based prospective cohort including genotype data, alcohol consumption, and potential confounding risk factors. Almost all the confounding factors that have been reported to be associated with the risk of COVID-19 are available in the UK Biobank. Ther...

    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

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  3. Version published to 10.1101/2020.11.25.20238915 on medRxiv