Investigating the link between SARS-CoV-2 infection and gastrointestinal illness using advanced linked data systems

Hawkings, Michael (2025) Investigating the link between SARS-CoV-2 infection and gastrointestinal illness using advanced linked data systems PhD thesis, University of Liverpool.

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Abstract

COVID-19 is now recognised as a significant multi-system illness with the potential to cause gastrointestinal manifestations. Since its emergence in 2019, initial case reports have evolved into large-scale studies suggesting possible long-term gastrointestinal sequelae. Conditions such as inflammatory bowel disease (IBD), coeliac disease (CD), irritable bowel syndrome (IBS) and acute gastroenteritis (AGE) share infection as a proposed trigger, and early evidence indicates that COVID-19 may carry an increased risk for their development. We conducted a series of interlinked studies to investigate the associations between COVID-19 and subsequent IBD, CD, IBS and AGE risk using routinely collected healthcare data from the Clinical Practice Research Datalink (CPRD). This dataset integrates information from primary care consultations, hospital admissions, and COVID-19-related ITU/HDU admissions. We also investigated the impact of SARS-CoV-2 vaccination on IBD, CD, IBS and AGE risk. A systematic review of the literature identified a higher prevalence of persistent gastrointestinal symptoms in individuals with a history of COVID-19 (10.8% compared with 4.9% in healthy controls), and an increased risk of illnesses including IBS, dyspepsia, hepatic disease, and autoimmune-mediated gastrointestinal disorders. In a retrospective cohort study of 800,000 patients, Cox regression identified an increased risk of incident IBD in patients hospitalised with COVID-19 (aHR 1.89 [95% CI: 1.36–2.61]) but no significant association for CD (aHR 1.92 [95% CI: 0.63–5.78]). No increased risk of incident CD (aHR 0.78 [95% CI: 0.57–1.07]) or IBD (aHR 1.02 [95% CI: 0.87–1.20]) was observed in community-managed COVID-19 cases. SARS-CoV-2 vaccination was associated with a reduced hazard of incident IBD (first-dose aHR 0.78 [95% CI: 0.67–0.91]), although there was no evidence that vaccination modified the association between COVID-19 exposure and IBD risk when modelled as an effect modifier. In a controlled interrupted time-series analysis, IBD incidence increased relative to a comparator condition following the onset of the COVID-19 pandemic, with an estimated 0.9% increase per month, providing additional population-level evidence supporting a potential association between the pandemic period and incident IBD. In a further cohort study investigating incident IBS and exacerbations of pre-existing IBS, we observed a reduced hazard of incident IBS in the community-positive cohort (aHR 0.84 [95% CI: 0.80–0.89]) and no significant association in hospitalised patients (aHR 0.71 [95% CI: 0.44–1.15]). COVID-19 exposure was also not associated with any significant change in the hazard of IBS exacerbations. These findings do not support an increased risk of incident IBS or exacerbations following COVID-19 infection and highlight the limitations of routine healthcare data for evaluating functional gastrointestinal disorders. A population-based rate analysis of AGE demonstrated a substantially increased rate among hospitalised COVID-19 patients (IRR 4.63 [95% CI: 4.15–5.17]) across multiple models, even after implementation of a three-month diagnostic lag period. This association persisted when compared with a matched cohort of patients hospitalised with sepsis. In contrast, community-managed COVID-19 cases demonstrated a modestly reduced AGE rate compared with test-negative controls. Overall, our findings suggest that moderate-to-severe COVID-19 may be associated with an increased risk of subsequent IBD and AGE, while no increased risk was observed for CD or IBS. The consistency of findings across both individual-level cohort analyses and population-level interrupted time-series analyses strengthens the evidence for a relationship between severe COVID-19 and subsequent IBD. We also identified a signal suggesting a potential protective effect between SARS-CoV-2 vaccination and incident IBD risk. These findings highlight the importance of continued follow-up of patients recovering from severe COVID-19 and demonstrate both the value and limitations of routinely collected healthcare data for investigating long-term infectious disease sequelae.

Item Type:	Thesis (PhD)
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Population Health Faculty of Health & Life Sciences > Inst. Population Health > Inst. Population Health
Depositing User:	Symplectic Admin
Date Deposited:	26 Aug 2026 08:26
Last Modified:	26 Aug 2026 08:26
DOI:	10.17638/03199027
Supervisors:	Buchan, Iain Hungerford, Dan Brierley, Liam Elliot, Alex Hughes, David Charalampopoulos, D
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3199027
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