Diagnosis of MIS-C in febrile children

发热儿童MIS-C的诊断

• 批准号: 10732879
• 负责人: Hamid Bassiri
• 金额: $ 156.54万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10732879
• 关键词: 2019-nCoV; Academy; Acute; Adult; American; Analytical Chemistry; Benign; Biological Markers; COVID-19; COVID-19 pandemic; Canis familiaris; Caring; Cessation of life; Characteristics; Child; Child Care; Childhood; Clinical; Clinical Pathways; Clinical Research; Consultations; Data; Development; Diagnosis; Diagnostic; Disease; Ensure; Epidemiology; Fever; Future; Goals; Guidelines; Health system; Immune; Immunoglobulin G; Immunologics; Immunology; Immunophenotyping; Infection; Inflammatory; Laboratories; Machine Learning; Mass Spectrum Analysis; Multisystem Inflammatory Syndrome in Children; Organ; Patients; Pediatric Hospitals; Pediatrics; Pennsylvania; Performance; Phase; Philadelphia; Positioning Attribute; Public Health; Publishing; Rapid diagnostics; Reporting; Reproducibility; Research; SARS-CoV-2 infection; Saliva; Salivary; Sampling; Severity of illness; Solid; Specificity; Syndrome; Training; Universities; Urine; Validation; Viral; Volatilization; Work; biomarker discovery; candidate identification; clinical diagnostics; clinical epidemiology; diagnostic strategy; diagnostic tool; global health; improved; member; metabolome; metabolomics; novel; pediatric patients; post-COVID-19; prospective; respiratory; response; seropositive; systemic inflammatory response; translational study; validation studies; volatile organic compound

PROJECT SUMMARY The recent emergence of SARS-CoV-2 and resultant pandemic of COVID-19 disease has overwhelmed global health systems and led to over 200,000 American deaths to date. While initial reports suggested that SARS- CoV-2 infection in children was generally benign, a novel post-inflammatory syndrome known as multisystem inflammatory syndrome in children (MIS-C) has now been described. MIS-C in children is characterized by fever, systemic inflammation, and end-organ involvement, and the majority of patients are IgG seropositive for SARS- CoV-2. Because the clinical features of MIS-C overlap with other infections and inflammatory disorders, new strategies for diagnosis of MIS-C in febrile children are urgently needed. Our immediate objective (during the R61 phase) is to determine the reproducible changes in breath, urine, and salivary volatile composition in chil- dren diagnosed with MIS-C. We will integrate these discovery studies with clinical and immunological profiling to develop (during R61 phase) and validate (during R33 phase) a novel and much-needed MIS-C diagnostic, which is expected to have a major impact on care of febrile children. Our long-term goal to develop a diagnostic strategy to distinguish children with MIS-C from children with other causes of fever. Supported by our strong preliminary data that indicate our expertise and feasibility of this strategy, our objectives will be met through three specific aims: 1) Characterize breath biomarkers in children with MIS-C (R61); 2) Relate breath VOC changes to virolog- ical, disease severity, and immunological features of MIS-C (R61); and 3) Validate our novel MIS-C diagnostic for clinical use (R33). The proposed research is significant, because we will progress in development of new, much-needed MIS-C rapid diagnostic tool.

项目摘要 最近出现的SARS-CoV-2和由此导致的COVID-19疾病大流行使全球 到目前为止，已经导致超过20万美国人死亡。虽然最初的报告显示SARS- 儿童中的CoV-2感染通常是良性的，这是一种称为多系统的新型炎症后综合征。 现在已经描述了儿童炎性综合征（MIS-C）。儿童MIS-C的特征是发热， 全身性炎症和终末器官受累，大多数患者的SARS IgG血清反应呈阳性- 二型冠状病毒由于MIS-C的临床特征与其他感染和炎症性疾病重叠，因此新的 因此迫切需要对发热儿童MIS-C的诊断策略。我们的近期目标（ R61阶段）是为了确定呼吸，尿液和唾液挥发性成分在儿童中的可重复变化。 诊断为MIS-C。我们将把这些发现研究与临床和免疫学分析相结合， 开发（在R61阶段）和验证（在R33阶段）一种新的和急需的MIS-C诊断， 预计将对发热儿童的护理产生重大影响。我们的长期目标是制定诊断策略 区分MIS-C患儿和其他发热原因患儿。在我们强大的初步支持下， 这些数据表明我们的专业知识和这一战略的可行性，我们的目标将通过三个具体的 目的：1）描述MIS-C（R61）儿童的呼吸生物标志物; 2）将呼吸VOC变化与病毒日志相关。 MIS-C（R61）的临床、疾病严重程度和免疫学特征;以及3）验证我们的新MIS-C诊断 临床使用（R33）。拟议的研究是重要的，因为我们将在开发新的， 急需的MIS-C快速诊断工具。