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Related Experiment Video

Updated: Oct 10, 2025

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Interleukin-18 and COVID-19.

C M Schooling1,2, M Li1, S L Au Yeung1

  • 1Li Ka Shing Faculty of Medicine, School of Public Health, The University of Hong Kong, Hong Kong SAR, China.

Epidemiology and Infection
|December 16, 2021
PubMed
Summary

Higher levels of interleukin-18, a key interferon precursor, were linked to a reduced risk of COVID-19, including severe cases. This suggests interleukin-18 may be a target for preventing coronavirus disease (COVID-19).

Keywords:
COVID-19Mendelian randomisationevolutionary biologyinterleukin-18

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Area of Science:

  • Immunology
  • Genetics
  • Infectious Disease Epidemiology

Background:

  • Interferon gamma (IFNγ) immunity influences COVID-19 vulnerability.
  • Interleukin-18 (IL-18) is a key modifiable precursor to IFNγ.

Purpose of the Study:

  • To investigate the association between genetically predicted interleukin-18 and COVID-19 risk, overall and by severity.
  • To explore potential associations with IFNγ, interleukin-12, and interleukin-23.

Main Methods:

  • Utilized Mendelian randomization with four genetic predictors for interleukin-18.
  • Applied data from a large genome-wide association study of COVID-19 (June 2021) including over 2.5 million individuals.
  • Performed inverse variance weighted analyses for COVID-19 of any severity, hospitalized, and very severe cases.

Main Results:

  • Genetically predicted interleukin-18 was associated with a lower risk of any COVID-19 (OR 0.96) and very severe COVID-19 (OR 0.88).
  • Sensitivity analyses supported these findings.
  • No significant associations were found for IFNγ, interleukin-12, or interleukin-23 due to limited genetic predictors.

Conclusions:

  • Interleukin-18 may be a modifiable target for preventing COVID-19.
  • Further experimental research on interleukin-18 is warranted.