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.

肠易激综合症 (IBS) 影响着大约 10-15% 的美国人口，并导致形态学和 生理异常严重损害一个人的生活质量，是最常见的诊断 肠-脑相互作用的胃肠道疾病 (DGBI) 的异质组 肠易激综合症 (IBS) 的风险。 急性胃肠道 (GI) 感染率约为 9%，与许多细菌、原生动物、 值得注意的是，SARS-CoV-2 感染会引发多种胃肠道症状，包括腹泻、 恶心和呕吐，据初步研究显示，高达 61% 的患者出现急性胃肠道症状。 40-44% 的 SARS-CoV-2 患者在急性感染后表现出持续性胃肠道症状可持续长达 5-6 个月。 鉴于当前大流行的规模以及急性 SARS-CoV-2 感染后慢性胃肠道症状的报道， 确定这种病原体将如何影响 IBS 症状的发生或恶化，同时发挥重要作用 在急性后 SARS-CoV-2 (PASC)（俗称“长新冠病毒”）的发展过程中，抗病毒治疗势在必行。 然而，迄今为止，缺乏评估急性后胃肠道疾病发展的研究 亚利桑那州 CoVHORT 是一项正在进行的前瞻性纵向研究，旨在追踪 SARS-CoV-2 感染后的情况。 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 我们建议使用该队列基础设施来有效调查这一流行病的健康影响。 目标如下：(1) 与非感染者相比，估计 SARS-CoV-2 感染后 IBS 的发病率 为了确定 SARS-CoV-2 感染后 IBS 的发病率，我们将使用数据。 罗马 IV IBS 诊断问卷，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，对那些未检测出 SARS-CoV-2 阳性的人进行检测， 性别、种族合并症以及感染时的伴随压力 (2) 确定感染时的作用。 我们将跟踪报告 IBS 的参与者的 PASC 的发展和严重程度。 (1) 2020 年 3 月之前诊断，(2) 感染 SARS-CoV-2 之前，以及 (3) 没有报告感染史的人 感染以确定其 2-5 年内持续和长期的症状，包括评估危险因素 (3) 建立 SARS-CoV-2 感染后 IBS 的机制，包括差异。 在粪便微生物组的组成和功能中，宿主对粪便微生物组的抗共生免疫反应 SARS-CoV-2 暴露者和接触者中的粪便微生物组和靶向/非靶向血清蛋白生物标志物 我们将收集血液和粪便样本并雇用。 鸟枪法宏基因组学、宿主微生物组定向 IgG-seq 和 IgA-seq 以及高维血清蛋白质组学 探索与 PASC-IBS 相关的新机制、表型和生物标志物的阵列将产生影响。 未来几年数百万美国人的个人健康状况，迄今为止，有限的研究 特别研究了 SARS-CoV-2 对胃肠道结果的潜在长期影响。