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 SARS-COV-2和COVID-19疾病的最新出现和导致的大流行使全球不堪重负 迄今为止，卫生系统并导致了200,000多人死亡。最初的报告表明SARS- 儿童中的COV-2感染通常是良性的，一种新型炎症后综合征称为多系统 现在已经描述了儿童炎症综合征（MIS-C）。儿童中的MIS-C的特征是发烧， 全身性炎症和末期受累，大多数患者对SARS- COV-2。因为MIS-C的临床特征与其他感染和炎症性疾病重叠，所以 迫切需要急需诊断为高热儿童的MIS-C的策略。我们的直接目标（在 R61相）是确定CHIL-呼吸，尿液和唾液挥发性成分的可重复变化 被诊断为MIS-C。我们将将这些发现研究与临床和免疫学分析整合到 开发（在R61阶段）并验证（在R33期间）一种新颖且急需的MIS-C诊断，该诊断 预计将对热热儿童的照顾产生重大影响。我们制定诊断策略的长期目标 将MIS-C的儿童与其他发烧原因的儿童区分开。由我们强大的初步支持 表明我们的专业知识和可行性的数据，我们的目标将通过三个特定 目的：1）表征MIS-C儿童的呼吸生物标志物（R61）； 2）将VOC的呼吸变化与病毒学变化 - MIS-C的疾病严重程度和免疫学特征（R61）； 3）验证我们的新型MIS-C诊断 用于临床使用（R33）。拟议的研究很重要，因为我们将在新的发展方面取得进展 急需的MIS-C快速诊断工具。