Critical COVID-19, Victivallaceae Abundance, and Celiac Disease: A Mediation Mendelian Randomization Study

People report persistent post-coronavirus disease 2019 (COVID-19) symptoms, but it is not known whether COVID-19 impacts celiac disease. The two-step Mendelian randomization (MR) method used was intended to investigate the causal genetic relationship between COVID-19 and celiac disease through gut microbiota. The largest celiac disease genome-wide association study was used to evaluate the impact of COVID-19 on the gut microbiota Victivallaceae and the associated genetic instrumental variants on celiac disease. Using a two-step MR, it was feasible to determine the following: 1) the causal effects of COVID-19 infection, hospitalized COVID-19, and critical COVID-19 on celiac disease; 2) the causal effects of gut microbiota, Victivallaceae, on celiac disease; and 3) the mediating effects of gut microbiota, Victivallaceae. We discovered that a higher critical COVID-19 was correlated to a higher risk of Celiac disease (inverse variance weighted [IVW], p=0·035; weighted median, p=0·035). We also found a negative correlation between critical COVID-19 and Victivallaceae abundance (IVW, p=0·045; weighted median, p=0·036), as well as a negative association between Victivallaceae abundance and celiac disease (IVW, p=0·016; weighted median, p=0·031). Our analysis provides genetic evidence that higher COVID-19 is causally connected with lower Victivallaceae abundance, which increases the risk of celiac disease.Funding: This study was supported by the National key research and development program (grant number: 2022YFF0710800).Declaration of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.