Investigating the impact of SARS-CoV-2 on gastrointestinal illness using advanced linked data systems

Study type
Protocol
Date of Approval
Study reference ID
23_002987
Lay Summary

COVID-19 is a complex illness which can cause a wide range of symptoms. We know that around one in five people with COVID-19 will experience stomach & bowel issues such as diarrhoea. We also know that the virus that causes COVID-19 can negatively affect our bowel health. Currently, there are thought to be millions of people suffering from persistent symptoms after having COVID-19. There is some evidence to suggest that people suffering from ‘long-COVID’ may have symptoms like diarrhoea, and that some individuals may be more prone to developing illnesses that affect our bowel after having COVID-19.

Research investigating the long-lasting impact of COVID-19 on our bowel health is relatively weak, so we can’t currently say who might be affected. Our study aims to investigate the relationship between a positive COVID-19 test and patients seeking care for stomach & bowel complaints. We are asking the question, do people infected with COVID-19 have an increased risk of stomach bugs and longer-term bowel problems?

We will use anonymised routine healthcare records from patients in the UK. We will look for GP consultations and hospital records for symptoms like diarrhoea, and for conditions like gastroenteritis (‘a stomach bug’). We will also look at diagnoses in a patient’s medical record for illnesses such as irritable bowel syndrome, inflammatory bowel disease and coeliac disease. Our study may show whether bowel issues are more common in individuals who have previously had COVID-19, whether vaccination affects this risk, and support researchers in developing future treatments.

Technical Summary

To investigate the impact of SARS-CoV-2 infection on healthcare attendances for gastrointestinal symptoms and the incidence of acute gastroenteritis (AGE), gastrointestinal infections, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and coeliac disease (CD) in the general population.

Objectives:

To assess whether SARS-CoV-2 infection:
1. has any impact on the rates of AGE;
2. is associated with autoimmune mediated gastrointestinal illness;
3. is associated with functional gastrointestinal illness.

Design: cohort study and interrupted time series analysis.

Population: any age, from March 2020 (January 2015 for interrupted time series analysis).

Exposure: SARS-CoV-2.

Primary outcomes: CPRD recorded primary care consultations for AGE and gastrointestinal infections; Hospital Episode Statistic recorded hospitalisation with AGE; Primary care and hospitalisations with a diagnosis of: irritable bowel syndrome, inflammatory bowel disease and coeliac disease diagnoses.

Confounders and adjusters: comorbidity, antimicrobial prescribing, SARS-CoV-2 vaccination status, socioeconomic deprivation, ethnicity, geography.

Data analysis: our cohort will comprise participants reporting a SARS-CoV-2 RT-PCR result during the study period. Test-positive and test-negative participants will be enrolled in the cohort from March 2020. A time-to-event analysis will be conducted using Cox proportional hazards models and flexible parametric survival models to estimate hazard ratios for incident gastrointestinal outcomes.

Interrupted time series analysis of incident IBD and CD cases will be conducted for the period March 2020 to December 2023, and the pre-COVID period of January 2015 to February 2020. A synthetic control cohort will be constructed to account for changes in healthcare-seeking behaviour throughout the pandemic.

This study may demonstrate acute and chronic gastrointestinal illness and autoimmune illness as sequalae to SARS-CoV-2 infection. It could also provide evidence supporting pubic health behaviours around preventing respiratory infections and SARS-CoV-2 vaccination. The results may also support the development of clinical guidelines and potential treatments for such illnesses.

Health Outcomes to be Measured

Primary care consultations for AGE.
Hospitalisations for AGE.
Primary care and hospitalisation with a diagnosis of IBD.
Primary care and hospitalisation with a diagnosis of CD.
Primary care and hospitalisation with a diagnosis of IBS.
HES Accident & Emergency attendances for gastrointestinal complaints.

Collaborators

Daniel Hungerford - Chief Investigator - University of Liverpool
Michael Hawkings - Corresponding Applicant - University of Liverpool
Alex Elliot - Collaborator - UK Health Security Agency (UKHSA)
DIMITRIOS CHARALAMPOPOULOS - Collaborator - University of Liverpool
Iain Buchan - Collaborator - University of Liverpool
Liam Brierley - Collaborator - University of Liverpool
Pieta Schofield - Collaborator - University of Liverpool

Linkages

CHESS (Hospitalisation in England Surveillance System);HES Accident and Emergency;HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;SGSS (Second Generation Surveillance System);COVID-19 Linkages