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

肠易激综合征(IBS)影响大约10%-15%的美国人口，并导致形态和 生理异常显著损害一个人的生活质量，是一种最常见的 胃肠-脑相互作用异质性胃肠病组(DGBI)。肠易激综合征的风险 急性胃肠道(GI)感染约占9%，并与许多细菌、原虫、 和病毒感染。值得注意的是，SARS-CoV-2感染引起广泛的胃肠道症状，包括腹泻， 恶心和呕吐，据报道高达61%的患者出现急性胃肠道症状。初步研究表明 在40-44%的SARS-CoV-2患者中，急性感染后持续胃肠道症状的时间长达5-6个月。 鉴于目前疫情的规模，以及急性SARS-CoV-2感染后出现慢性胃肠道症状的报道， 确定这种病原体将如何影响发病率或加剧IBS症状，同时发挥主要作用 在后急性SARS-CoV-2(PASC)的发展过程中，俗称Long COVID是势在必行的。 然而，到目前为止，很少有研究评估急性后胃肠道疾病的发展。 在感染SARS-CoV-2之后。亚利桑那州CoVHORT，一项正在进行的前瞻性纵向研究 SARS-CoV-2感染对成人的急性和长期影响，提供了关键的现有基础设施 有效地调查大流行对健康的影响所需的。使用这一队列基础设施，我们建议 以下目标：(1)估计感染SARS-CoV-2后IBS的发病率与非SARS-CoV-2感染后IBS的发病率 受感染的参与者。为了确定SARS-CoV-2感染后IBS的发生率，我们将使用数据 来自罗马IV IBS诊断问卷，以比较以下参与者的新发IBS发生率 在控制年龄等混杂因素的同时，对没有检测到SARS-CoV-2的人检测出SARS-CoV-2阳性， 感染时的性别、种族、共病和伴随的压力。(二)明确角色定位 先前存在的IBS对PASC的发展和严重程度的影响。我们将追踪那些报告了 诊断(1)在2020年3月之前，(2)在感染SARS-CoV-2之前，以及(3)报告没有 在2-5年期间确定感染的持续和长期症状，包括评估风险因素 和混血儿。(3)建立SARS-CoV-2感染后IBS的发病机制，包括差异 在粪便微生物群的组成和功能上，宿主的反共生免疫反应 暴露于SARS-CoV-2和非SARS-CoV-2人群中的粪便微生物群和靶向/非靶向血清蛋白生物标志物 未暴露者，发生和不发生IBS的人。我们将采集血液和粪便样本，并聘请 鸟枪式元基因组学、宿主微生物组导向的免疫球蛋白序列和免疫球蛋白A序列以及高维血清蛋白质组 探索与PASC-IBS相关的新机制、表型和生物标记物。PASC将影响 未来几年数百万美国人的个人健康状况，到目前为止，研究还很有限 具体研究了SARS-CoV-2对胃肠道疾病结局的潜在长期影响。

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.