Determining the Incidence, Risk Factors and Biological Drivers of Irritable Bowel Syndrome (IBS) as Part of the Constellation of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Outcomes

Irritable bowel syndrome (IBS) affects an estimated 10-15% of the U.S population and induces morphologic and physiological abnormalities significantly impairing one's quality of life and is the most common diagnosis of a heterogeneous group of gastrointestinal disorders of gut-brain interaction (DGBI). The risk of IBS following an acute gastrointestinal (GI) infection is approximately 9%, and has been linked to numerous bacterial, protozoan, and viral infections. Notably, SARS-CoV-2 infection elicits a wide range of GI symptoms, including diarrhea, nausea, and vomiting, with reports of acute GI symptoms occurring in up to 61% of patients. Initial studies have shown persistent GI symptoms lasting up to 5-6 months post-acute infection in 40-44% of SARS-CoV-2 patients. Given the scale of the ongoing pandemic and reports of chronic GI symptoms after acute SARS-CoV-2 infection, determining how this pathogen will impact the incidence or exacerbate IBS symptoms, while playing a major role in the development of post-acute SARS-CoV-2 (PASC), known colloquially as Long COVID, is imperative. However, to date, there is a dearth of studies that have assessed the development of post-acute GI disorders following SARS-CoV-2 infection. The Arizona CoVHORT, an ongoing, prospective, longitudinal study of the acute and long-term impacts of SARS-CoV-2 infection on adults, provides the critical extant infrastructure required to efficiently investigate the health impacts of the pandemic. Using this cohort infrastructure, we propose the following aims: (1) Estimate the incidence of IBS following SARS-CoV-2 infections compared to non- infected participants. To determine the incidence of IBS following SARS-CoV-2 infection, we will employ data from the Rome IV IBS diagnostic questionnaire to compare rates of new onset IBS among participants who tested positive for SARS-CoV-2 to those who did not, while controlling for confounding factors such as age, gender, and ethnicity comorbidities and concomitant stress at the time of infection. (2) Determine the role of pre-existing IBS on the development and severity of PASC. We will follow IBS participants who reported a diagnosis (1) prior to March 2020, (2) before a SARS-CoV-2 infection, and (3) those who report no history of infection to determine their ongoing and long-term symptoms over 2-5 years, including assessment of risk factors and confounders. (3) Establish mechanisms of IBS following SARS-CoV-2 infections including differences in the fecal microbiome composition and function, the host's anti-commensal immune response to the fecal microbiome, and targeted/untargeted serum protein biomarkers among SARS-CoV-2 exposed and unexposed, who do and do not develop incident IBS. We will collect blood and stool samples and employ shotgun metagenomics, host-microbiome directed IgG-seq and IgA-seq, and high dimensional serum proteomic arrays to explore novel mechanisms, phenotypes, and biomarkers associated with PASC-IBS. PASC will impact the individual health of millions of Americans over the next several years, and to date, limited studies have examined potential long-term effects of SARS-CoV-2 on GI outcomes specifically.