Irritable bowel syndrome (IBS) affects an estimated 10-15% of the U.S population and induces morphologic andphysiological abnormalities significantly impairing ones quality of life and is the most common diagnosis of aheterogeneous group of gastrointestinal disorders of gut-brain interaction (DGBI). The risk of IBS following anacute gastrointestinal (GI) infection is approximately 9% and has been linked to numerous bacterial protozoanand viral infections. Notably SARS-CoV-2 infection elicits a wide range of GI symptoms including diarrheanausea and vomiting with reports of acute GI symptoms occurring in up to 61% of patients. Initial studies haveshown 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 infectiondetermining how this pathogen will impact the incidence or exacerbate IBS symptoms while playing a major rolein 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 disordersfollowing SARS-CoV-2 infection. The Arizona CoVHORT an ongoing prospective longitudinal study of theacute and long-term impacts of SARS-CoV-2 infection on adults provides the critical extant infrastructurerequired to efficiently investigate the health impacts of the pandemic. Using this cohort infrastructure we proposethe 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 datafrom the Rome IV IBS diagnostic questionnaire to compare rates of new onset IBS among participants whotested positive for SARS-CoV-2 to those who did not while controlling for confounding factors such as agegender and ethnicity comorbidities and concomitant stress at the time of infection. (2) Determine the role ofpre-existing IBS on the development and severity of PASC. We will follow IBS participants who reported adiagnosis (1) prior to March 2020 (2) before a SARS-CoV-2 infection and (3) those who report no history ofinfection to determine their ongoing and long-term symptoms over 2-5 years including assessment of risk factorsand confounders. (3) Establish mechanisms of IBS following SARS-CoV-2 infections including differencesin the fecal microbiome composition and function the hosts anti-commensal immune response to thefecal microbiome and targeted/untargeted serum protein biomarkers among SARS-CoV-2 exposed andunexposed who do and do not develop incident IBS. We will collect blood and stool samples and employshotgun metagenomics host-microbiome directed IgG-seq and IgA-seq and high dimensional serum proteomicarrays to explore novel mechanisms phenotypes and biomarkers associated with PASC-IBS. PASC will impactthe individual health of millions of Americans over the next several years and to date limited studies haveexamined potential long-term effects of SARS-CoV-2 on GI outcomes specifically.