Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank

  1. Xikang Fan
  2. Cheng Yin
  3. Jiayu Wang
  4. Mingjia Yang
  5. Hongxia Ma
  6. Guangfu Jin
  7. Mingyang Song
  8. Zhibin Hu
  9. Hongbing Shen
  10. Dong Hang

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Abstract

Background

Coronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown.

Objective

To investigate the association between circulating IGF-1 concentrations and mortality risk among COVID-19 patients.

Design

Prospective analysis.

Setting

UK Biobank.

Participants

1425 COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006-2010).

Main outcome measures

COVID-19 mortality (available death data updated to 22 May 2020). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality across the IGF-1 quartiles.

Results

Among 1425 COVID-19 patients, 365 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 37% lower risk of mortality (OR: 0.63, 95% CI: 0.43-0.93, P -trend=0.03). The association was stronger in women and nonsmokers (both P -interaction=0.01).

Conclusions

Higher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.09.20149369: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableStratified analyses were conducted according to the median age at infection (<70, ≥70 years), sex (male, female), BMI (<30, ≥30 kg/m2), physical activity (≤median, >median), and smoking status (never, ever) in the fully-adjusted model.

    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:
    Several potential limitations also need to be acknowledged. First, the observational nature of this study prevents us from inferring causality. However, our sensitivity analyses excluding baseline CVD and cancer supported the robustness of the findings. Second, given the lack of repeated IGF-1 measurements, we were unable to analyze the relationship between dynamic IGF-1 concentrations and COVID-19 mortality. However, we calculated the intraclass correlation coefficient (ICC) between IGF1 measurements collected 4 years apart in a subcohort (n= 16,356). The ICC value of 0.78, consistent with the previous data 19, indicates that IGF1 levels are generally stable over time. Third, due to limited coverage of coronavirus testing in the UK, ascertainment bias cannot be avoided. In addition, UK Biobank is not a representative sample of the UK population 20, limiting ability to generalize the results to the whole UK or other populations.

    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.

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  2. Version published to 10.1101/2020.07.09.20149369v1 on medRxiv