Identifying biomarker signatures of prognostic value for Multisystem Inflammatory Syndrome in Children (MIS-C)

识别儿童多系统炎症综合征 (MIS-C) 预后价值的生物标志物特征

• 批准号: 10651536
• 负责人: MICHAEL A LYNES
• 金额: $ 19.52万
• 依托单位: CONNECTICUT CHILDREN'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10651536
• 关键词: 2019-nCoV; Acute; Acute Renal Failure with Renal Papillary Necrosis; Acute Respiratory Distress Syndrome; Adipose tissue; Adolescent; Adult; Antibodies; Antibody Affinity; Antibody Repertoire; Antibody Response; Asthma; Attention; Biological; Biological Assay; Biological Markers; Biological Products; Biosensor; Blood Vessels; COVID-19; COVID-19 diagnosis; COVID-19 patient; COVID-19 severity; Cardiac; Child; Childhood; Clinical; Collaborations; Colombia; Coupled; Development; Diagnostic; Disease; Elderly; Enrollment; Environmental Exposure; Epidemiology; Epigenetic Process; Epitopes; Exhibits; Flow Cytometry; Fluorescence; Generations; Genetic; Grant; Growth; Gut Mucosa; Humoral Immunities; Immune; Immune response; Immunoglobulin G; Immunologics; Infection; Inflammatory; Inflammatory Bowel Diseases; Intervention Studies; Kinetics; Laboratories; Libraries; Measures; Mechanical ventilation; Mind; Molecular; Molecular Conformation; Mucocutaneous Lymph Node Syndrome; Multisystem Inflammatory Syndrome in Children; Neurosecretory Systems; Nucleocapsid; Obesity; Oral; Outcome; Parents; Patient-Focused Outcomes; Patients; Phage Display; Pharmaceutical Preparations; Population; Proteins; RADx; RNA vaccination; RNA vaccine; Respiratory distress; Risk; SARS-CoV-2 antibody; SARS-CoV-2 exposure; SARS-CoV-2 genome; SARS-CoV-2 infection; SARS-CoV-2 spike protein; SARS-CoV-2 variant; Surface Plasmon Resonance; Symptoms; Syndrome; Technology; Testing; Thrombosis; Time; United States; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Variant; Viral Pneumonia; Virus; accurate diagnosis; acute infection; biomarker discovery; biomarker signature; care outcomes; cerebrovascular; cohort; cost; cross reactivity; diagnostic algorithm; diagnostic value; fight against; gut microbiome; gut-brain axis; improved; minority children; mortality; neutralizing antibody; novel coronavirus; plasmonics; post SARS-CoV-2 infection; prognostic; prognostic algorithm; prognostic value; prognostication; programs; response; risk stratification; severe COVID-19; treatment strategy; young adult

PROJECT SUMMARY / ABSTRACT – No Changes From the Original Application In adults, SARS-CoV-2 infection exhibits a wide range of clinical outcomes, from asymptomatic and mild disease to severe viral pneumonia, respiratory distress, acute kidney injury, thrombotic disorders, and serious cardiac, cerebrovascular and vascular complications. Severe infection can also occur both in children and young adults (< 21), and a significant proportion of children admitted with Covid-19 require ICU support, frequently including mechanical ventilation. In addition, children and adolescents with initially asymptomatic SARS-CoV-2 infection have presented with a rare, but very severe multisystem inflammatory syndrome (MIS-C). Epidemiologic, clinical and laboratory predictors of progression towards severe forms of acute infection with SARS-CoV-2 and MIS-C are thus urgently needed in the fight against Covid-19 in this population. As defined in the NIH Rapid Acceleration of Diagnostics (RADx) program, biomarker discovery can enable risk stratification and guide interventional studies to target Covid-19 patients at enhanced risk of developing complications and/or severe disease. To target this discovery initiative, herein we will use a battery of biological, immunological and molecular tests, including Grating-Coupled Fluorescence Plasmonic (GCFP) and advanced flow cytometry, to study children and young adults (<21 years) with mild, moderate or severe SARS-CoV-2 infection. GCFP allows the use of disposable biosensor chips that can be mass-produced at low cost and spotted in microarray format to greatly increase multiplexing capabilities. In addition, we will use a similar biomarker approach for rapid differentiation of patients with MIS-C versus other pediatric infectious or inflammatory conditions where the clinical presentation resembles MIS-C, most importantly Kawasaki disease. A child's biologic and immunologic response to SARS-CoV-2 exposure is likely influenced by a variety of factors, including genetics, epigenetics and products of the mucosa/gut-brain axis, adipose tissue and neuroendocrine immune network, and further modulated by environmental exposures. With these factors in mind, we hypothesize that a child's biomarker profile in response to SARS-CoV-2 infection enables a timely and accurate prediction of severity of Covid-19 and diagnosis of MIS-C, and will help guide treatment strategies, and predict patient outcomes. To test this hypothesis, we will use a non-traditional diagnostic and comprehensive biomarker discovery to characterize the clinical and laboratory spectrum of children and adolescents with mild, moderate and severe SARS-CoV-2 infection, as well as MIS-C. We will then validate our newly developed diagnostic and prognostic algorithm to distinguish MIS-C from other inflammatory disorders with overlapping clinical manifestations, including Kawasaki disease, and predict the longitudinal risk of complications.

项目摘要/摘要 – 与原始应用程序相比没有变化 在成人中，SARS-CoV-2 感染表现出多种临床结果，从无症状到轻度疾病 严重的病毒性肺炎、呼吸窘迫、急性肾损伤、血栓性疾病和严重的心脏病， 儿童和年轻人也可能发生脑血管和血管并发症。 (< 21)，并且很大一部分因 Covid-19 入院的儿童需要 ICU 支持，通常包括 此外，最初无症状的 SARS-CoV-2 感染儿童和青少年。 患有一种罕见但非常严重的多系统炎症综合征（MIS-C）。 SARS-CoV-2 和 MIS-C 严重急性感染进展的实验室预测因素 因此，根据 NIH Rapid 的定义，在这一人群中迫切需要对抗 Covid-19。 诊断加速 (RADx) 计划、生物标志物发现可以实现风险分层和指导 针对出现并发症和/或重症风险较高的 Covid-19 患者的介入研究 为了针对这一发现举措，我们将使用一系列生物学、免疫学和分子学方法。 测试，包括光栅耦合荧光等离子体 (GCFP) 和先进的流式细胞术，以研究 患有轻度、中度或重度 GCFP 感染的儿童和年轻人（<21 岁）允许使用。 使用可以低成本大量生产并以微阵列形式发现的一次性生物传感器芯片 此外，我们将使用类似的生物标记方法进行快速检测。 MIS-C 患者与其他儿科感染性或炎症性疾病患者的区别 临床表现类似于 MIS-C，最重要的是儿童的生物学和免疫学。 对 SARS-CoV-2 暴露的反应可能受到多种因素的影响，包括遗传学、表观遗传学 以及粘膜/肠脑轴、脂肪组织和神经内分泌免疫网络的产物，以及进一步 考虑到这些因素，我们将其作为儿童的生物标志物。 针对 SARS-CoV-2 感染的分析能够及时准确地预测 Covid-19 的严重程度 和 MIS-C 的诊断，将有助于指导治疗策略，并预测患者的结果来测试这一点。 假设，我们将使用非传统的诊断和全面的生物标志物发现来表征 患有轻度、中度和重度 SARS-CoV-2 的儿童和青少年的临床和实验室谱 然后我们将验证我们新开发的诊断和预后算法。 将 MIS-C 与其他临床表现重叠的炎症性疾病（包括川崎病）区分开来 疾病，并预测并发症的纵向风险。

项目成果

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.

使用光栅耦合荧光等离子体微阵列开发生物标志物特征，用于诊断 MIS-C。

• 发表时间: 2023
• 作者: Maltz;Melchiorre, Clare K;Herbst, Katherine W;Hogan, Alexander H;Dibble, Kristina;O'Sullivan, Brandon;Graf, Joerg;Jadhav, Aishwarya;Lawrence, David A;Lee, William T;Carson, Kyle J;Radolf, Justin D;Salazar, Juan C;Lynes, Mi
• 通讯作者: Lynes, Mi

Going Viral: Assessing the Impact of Social Media on Enrollment in a Coronavirus Disease 2019 (COVID-19) Cohort Study.

病毒式传播：评估社交媒体对 2019 年冠状病毒病 (COVID-19) 队列研究的影响。

• 发表时间: 2024-03
• 作者: Hogan, Alexander H;Herbst, Katherine W;Defelice, Carlie;Schulman, Noah;Adams, Aaron M;Carroll, Christopher L;Salazar, Juan C
• 通讯作者: Salazar, Juan C

Durability of Immunity Is Low Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.1, BA.2, and BA.3 Variants After Second and Third Vaccinations in Children and Young Adults With Inflammatory Bowel Disease Receiving Biologics.

接受生物制剂治疗的炎症性肠病儿童和青少年在第二次和第三次疫苗接种后，对严重急性呼吸系统综合症冠状病毒 2 Omicron BA.1、BA.2 和 BA.3 变种的免疫力持续时间较低。

• 发表时间: 2022-12
• 影响因子: 29.4
• 作者: Bellusci, Lorenza;Zahra, Fatema Tuz;Hopkins, Dena E;Salazar, Juan C;Hyams, Jeffrey S;Khurana, Surender
• 通讯作者: Khurana, Surender

Kawasaki Disease Hospitalizations in the United States 2016-2020: A Comparison of Before and During the Coronavirus Disease 2019 Era.

2016-2020 年美国川崎病住院人数：2019 年冠状病毒病之前和期间的比较。

• 发表时间: 2021-11-01
• 作者: Phamduy, Timothy T;Smith, Sharon;Herbst, Katherine W;Phamduy, Paul T;Brimacombe, Michael;Hogan, Alexander H;Salazar, Juan C;Sturm, Jesse
• 通讯作者: Sturm, Jesse