Celiac Disease and the Susceptibility of COVID-19 and the Risk of Severe COVID-19: A Mendelian Randomization Study

Previous observational studies have found that the susceptibility of COVID-19 and the risk of severe COVID-19 are not increased in patients with celiac disease (CeD). However, the findings of observational studies are prone to bias due to reverse causation and confounding, especially in the case of a newly-emerged disease. In this study, we aimed to further clarify the underlying relationship by both observational and Mendelian Randomization (MR) analysis.The observational study was conducted in the UK Biobank (UKB) cohort. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of COVID-19 susceptibility and severe COVID-19. To understand the causality between CeD and COVID-19 susceptibility and severe COVID-19, we performed a two-sample MR analysis.Our observational study showed that CeD patients had a lower susceptibility of COVID-19 (OR=0.699, p=0.006), while CeD was not significantly associated with severe COVID-19 (p>0.05). The findings from our MR study further demonstrated that the susceptibility to both COVID-19 (OR=0.963, p=0.006) and severe COVID-19 (OR=0.919, p=0.049) were lower in CeD patients, although the former seemed to be specific to the UKB cohort.Our results suggested that it may be unnecessary to take extra COVID-19 precaution in CeD patients.