Investigating the Causal Links between COVID-19 and Pancreatitis by
Bidirectional Mendelian Randomization
Abstract
Objective The immune response is a double-edged sword, and
COVID-19 shares similarities with pancreatitis in terms of natural
immune response, immune storm, and multi-organ involvement. However,
whether a causal association between them remained unclear. This study
aimed to investigate the potential causal association between COVID-19
and pancreatitis using a bidirectional Mendelian Randomization (MR)
approach. Methods The study analyzed three variables related to
COVID-19 (severity, hospitalization, and susceptibility) with a sample
size ranging from approximately 1,059,456 to 1,557,411. Additionally,
four types of pancreatitis (acute, chronic, alcohol-induced acute, and
chronic) were examined, with a sample size ranging from 337,126 to
377,277. Causal associations were estimated using inverse-variance
weighted (IVW), median weighted, and MR-Egger methods. Results
The IVW model indicated potential causal associations between genetic
susceptibility to severe and hospitalized COVID-19 and a decreased risk
of acute pancreatitis (OR = 0.914, p = 0.01; OR = 0.884, p = 0.008) and
alcohol-induced chronic pancreatitis (OR = 0.852, p = 0.013; OR = 0.768,
p = 0.002), including chronic pancreatitis. Inconsistent
associations were observed between IVW and sensitivity analyses in acute
and chronic pancreatitis of severe and hospitalized COVID-19.
Conversely, no significant associations were found between pancreatitis
traits and COVID-19-related variables in reverse MR analysis. No
heterogeneity or pleiotropy was found. Conclusions Host genetic
liability to severe and hospitalized COVID-19 was causally associated
with declining risk of alcohol-induced chronic pancreatitis, while no
significant association was observed for pancreatitis on COVID-19
outcomes. This study has significant implications for unraveling their
pathogenesis and guiding clinical management.