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

确定肠易激综合症 (IBS) 的发病率、危险因素和生物驱动因素作为 SARS-CoV-2 感染急性后遗症 (PASC) 结果的一部分

• 批准号: 10630409
• 负责人: Kristen M Pogreba-Brown
• 金额: $ 65.02万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630409
• 关键词: 2019-nCoV; Acute; Adult; Affect; Age; American; Arizona; Bacterial Infections; Biological; Biological Markers; Blood specimen; COVID-19 patient; Caregivers; Chronic; Critical Pathways; Data; Development; Diagnosis; Diagnostic; Diarrhea; Disease Progression; Enrollment; Enteric Nervous System; Ethnic Origin; Functional Gastrointestinal Disorders; Gastrointestinal Diseases; Gender; Health; Health Personnel; Immune response; Immunoglobulin A; Immunoglobulin G; Impairment; Incidence; Individual; Infection; Infrastructure; Investigation; Irritable Bowel Syndrome; Link; Long COVID; Long-Term Effects; Longitudinal cohort study; Metagenomics; Morbidity - disease rate; Morphology; Nausea; Outcome; Participant; Pathologic; Patients; Persons; Phenotype; Physiological; Play; Population; Post-Acute Sequelae of SARS-CoV-2 Infection; Proteomics; Protozoan Infections; Quality of life; Questionnaires; Recording of previous events; Reporting; Research; Risk; Risk Assessment; Risk Factors; Role; Rome; SARS-CoV-2 exposure; SARS-CoV-2 infection; SARS-CoV-2 positive; Serum; Serum Proteins; Severities; Shotguns; Stress; Symptoms; Testing; Time; Virus Diseases; Vomiting; acute infection; associated symptom; cohort; comorbidity; disorders of gut-brain interaction; experience; fecal microbiome; gastrointestinal; gastrointestinal infection; gastrointestinal symptom; gut inflammation; gut microbiome; high dimensionality; host microbiome; infection rate; long term consequences of COVID-19; longitudinal, prospective study; microbiome composition; mortality; multiple omics; novel; novel marker; pandemic disease; pandemic impact; pathogen; post SARS-CoV-2 infection; protein biomarkers; psychologic; stool sample

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.

肠易激综合征（IBS）影响美国人口的10-15％，并诱导形态学和 生理异常严重损害了一个人的生活质量，是最常见的诊断 肠道相互作用（DGBI）的胃肠道疾病的异质群。 IBS之后的风险 急性胃肠道（GI）感染约为9％，与许多细菌，原生动物有关 和病毒感染。值得注意的是，SARS-COV-2感染引起了广泛的GI症状，包括腹泻， 恶心和呕吐，有多达61％的患者发生急性GI症状的报道。最初的研究有 显示40-44％的SARS-COV-2患者急性感染后长达5-6个月的持续性胃肠道症状。 鉴于持续的大流行的规模以及急性SARS-COV-2感染后慢性GI症状的报道， 确定该病原体将如何影响事件或加剧IBS症状，同时发挥主要作用 在急诊后的急性SARS-COV-2（PASC）的发展中，俗称为长期的covid。 但是，迄今 SARS-COV-2感染后。亚利桑那州科沃特（Arizona Covhort）是一项持续的，前瞻性的纵向研究 SARS-COV-2感染对成人的急性和长期影响提供了关键的额外基础设施 有效研究大流行的健康影响所需。使用此队列基础架构，我们建议 以下目的：（1）估计SARS-COV-2感染后IBS的事件与非 - 受感染的参与者。为了确定SARS-COV-2感染后IB的事件，我们将采用数据 从罗马IV IB IBS诊断问卷调查，并比较参与者的新发作IB SARS-COV-2的测试呈阳性，但在控制年龄等混杂因素时未经测试的人 感染时性别和种族合并症和伴随的压力。 （2）确定 IBS的IBS关于PASC的发展和严重性。我们将关注报告的IBS参与者 诊断（1）在2020年3月之前，（2）在SARS-COV-2感染之前，（3）那些没有报告历史的人 感染以确定2 - 5年内其持续和长期症状，包括评估风险因素 和混杂的人。 （3）在SARS-COV-2感染后建立IBS的机制，包括差异 在粪便微生物组的组成和功能中，宿主对抗惯例的免疫反应 SARS-COV-2中的粪便微生物组和靶向/非靶向血清蛋白生物标志物暴露于 未暴露，他们做和不发展事件IBS。我们将收集血液和粪便样本，并采用 shot弹枪宏基因组学，宿主 - 微生物组指导IgG-Seq和IgA-Seq，以及高维血清蛋白质组学 探索与PASC-IB相关的新型机制，表型和生物标志物的阵列。 PASC将影响 在未来几年中，数百万美国人的个人健康，迄今为止，有限的研究已经 研究了SARS-COV-2对GI结果的潜在长期影响。