The impact of COVID-19 on gastrointestinal diseases in vaccinated and unvaccinated individuals: a population-based cohort study in England

BackgroundCOVID-19 is associated with higher rates of gastrointestinal diseases, though the duration of this effect, and the role of vaccination and COVID-19 severity remain uncertain. ObjectiveTo investigate the relationship between COVID-19 and gastrointestinal diseases, by vaccination status in hospitalised and non-hospitalised patients. DesignWith NHS England approval, OpenSAFELY-TPP was used to access linked data from 24 million English adults. We defined three cohorts: "Pre-vaccination" (January 2020-June 2021), "vaccinated" and "unvaccinated" (June-December 2021). We estimated adjusted hazard ratios (aHRs) comparing the incidence of 10 gastrointestinal diseases, including upper and lower gastrointestinal bleeding, after versus before or without a COVID-19 diagnosis overall and by COVID-19 severity. ResultsCOVID-19 diagnosis was associated with elevated incidence of gastrointestinal diseases, particularly after hospitalised disease. In the pre-vaccination cohort (n=18,422,781), the adjusted hazard ratios (aHRs) for upper gastrointestinal bleeding after hospitalised COVID-19 were 20.1 (95% CI 18.4-22.1) in weeks 1-4 and 1.90 (1.63-2.22) in weeks 53-102. The corresponding aHRs after non-hospitalised COVID-19 were 1.92 (1.74-2.11) and 1.34 (1.23- 1.45) respectively. Across time periods, aHRs for gastrointestinal diseases were lower in vaccinated (n=14,948,727) than in unvaccinated (n=3,479,043) individuals. These patterns were similar across gastrointestinal diseases. ConclusionThe incidence of gastrointestinal disease is elevated for up to two years among individuals hospitalised following a COVID-19 diagnosis. Increases in incidence are attenuated among vaccinated individuals. Monitoring for gastrointestinal diseases after severe COVID-19 and promotion of vaccination in vulnerable groups are key to reducing long-term burden. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAcute symptoms of COVID-19 include gastrointestinal problems, and there is existing evidence that those with a COVID-19 diagnosis are more likely to experience long-term gastrointestinal complications, especially if they were hospitalised. C_LIO_LIPrevious studies were either limited in size, lacked representativeness of the population, or had short follow-up (e.g. during hospitalisation). The role of vaccination, COVID-19 severity or peoples characteristics (e.g. age or sex) were not considered. C_LI What this study addsO_LIBased on population-wide data on 18.4 million individuals, rates of 10 gastrointestinal diseases are elevated after COVID-19, compared with rates before or without COVID-19 diagnosis. C_LIO_LIThe elevation in rates of gastrointestinal diseases after COVID-19 diagnosis was less marked in people who were vaccinated before COVID-19 diagnosis. C_LIO_LIThe elevation in rates was markedly higher, and persisted for up to two years, among individuals hospitalised with COVID-19, compared with those who were not hospitalised. C_LI How this study might affect research, practice or policyO_LIWe show for the first time that the incidence of both acute and chronic gastrointestinal diseases remains elevated for up to two years after severe COVID-19 leading to hospitalisation. C_LIO_LIOur findings highlight the protective role of COVID-19 vaccination in reducing severe COVID-19 and its subsequent long-term gastrointestinal complications, reinforcing the importance of vaccination as a public health measure. C_LIO_LIIndividuals who had severe COVID-19, regardless of vaccination status, should be prioritised for clinical monitoring for gastrointestinal diseases. C_LI