Frontiers in Pharmacology (Jun 2023)

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19

  • Hongfei Song,
  • Na Lei,
  • Ling Zeng,
  • Xiuyan Li,
  • Cen Jiang,
  • Quansheng Feng,
  • Yue Su,
  • Jibin Liu,
  • Jie Mu

DOI
https://doi.org/10.3389/fphar.2023.1171404
Journal volume & issue
Vol. 14

Abstract

Read online

Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics.Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR–Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship.Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01–1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87–0.97, p = 0.002).Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19.

Keywords