Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: A multinational population-based cohort study from South Korea, Japan, and the UK.

Background/aims: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of SARS-CoV-2 infection in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary diseases and other digestive abnormalities.

Methods: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). A total of 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years who had SARS-CoV-2 infection between 2020 and 2021 were matched to non-infected controls. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with controls.

Results: The discovery cohort revealed heightened risks of gastrointestinal diseases (HR 1.15; 95% CI 1.08-1.22), hepatobiliary diseases (HR 1.30; 95% CI 1.09-1.55), and other digestive abnormalities (HR 1.05; 95% CI 1.01-1.10) beyond the first 30 days of infection, after exposure-driven propensity score-matching. The risk was pronounced according to the COVID-19 severity. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. The risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort.

Conclusion: The incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.