Characterizing the Immune Response to COVID-19 Infection in Atopic Dermatitis

特应性皮炎对 COVID-19 感染的免疫反应特征

• 批准号: 10181688
• 负责人: Emma Guttman
• 金额: $ 24.46万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-04 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10181688
• 关键词: 18 year old; Adult; Affect; Africa; African; African American; American; Asia; Asian Americans; Asians; Atopic Dermatitis; Biological Markers; Biopsy; Blood; Blood specimen; Body Surface; Body Surface Area; Characteristics; China; Clinical; Cytokine Activation; DNA; Data; Defect; Development; Disease; Disease Progression; Enrollment; Epithelial Cell Aggregation and Separation; Ethnic Origin; Ethnic group; European; Flow Cytometry; Gene Expression; Genetic; Genetic Polymorphism; Genetic Risk; Genomics; Healthcare; Hyperplasia; IgE; Immune; Immune Targeting; Immunohistochemistry; Immunologic Markers; Inflammation; Interleukin-13; Interleukin-4; Investigation; Japan; Korea; Lesion; Location; Maps; Modality; Modeling; Molecular; Pathogenesis; Pathway interactions; Patients; Phenotype; Population; Prevalence; Pruritus; Psoriasis; Punch Biopsy; Quality of life; Quantitative Reverse Transcriptase PCR; RNA; Reporting; Resistance; Serum; Severities; Severity of illness; Skin; Sleep Deprivation; Sleep disturbances; Subgroup; Surface; Swab; Systemic disease; Systems Biology; T-Lymphocyte Subsets; Taiwan; Testing; Therapeutic; Topical agent; Widespread Disease; attenuation; base; chemokine; cytokine; ethnic difference; exome sequencing; genetic analysis; immune activation; improved; individualized medicine; innovation; interleukin-22; keratinocyte; microbiome; molecular phenotype; new therapeutic target; novel therapeutics; personalized medicine; response; risk variant; skin barrier; skin lesion; systemic inflammatory response; therapy development; transcriptome sequencing

Project Summary/Abstract Great efforts are made in the face of the pandemic to understand anti-viral immune responses to COVID-19/SARS-CoV-2. It is crucial to understand immune responses in moderate-to-severe atopic dermatitis (AD) patients who are on systemic immune-modulating medications and are infected with COVID-19. AD patients(with and without asthma), are at increased risk for viral infections. Characterizing responses to COVID-19 infection in AD patients may guide the way these patients are treated, and inform on whether treatments need to be modified or discontinued in the instance of asymptomatic or symptomatic infections. Although some studies have shown that Th2 cytokines (among other cytokines) are elevated in severely ill patients admitted to ICUs with pneumonia secondary to COVID-19, no efforts have been published thus far evaluating the role of Th2 inflammation in severity of symptoms and outcomes in patients with COVID-19. Furthermore, the incidence and severity of COVID-19 symptoms among patients receiving Th2 blockade for atopic dermatitis with dupilumab, a monoclonal antibody targeting the IL-4/IL-13 signaling IL-4R receptor alpha subunit, has not been evaluated. It has long been believed that abnormally elevated Th2-axis polarization in the setting of AD and asthma patients may negatively impact the ability of the immune system to induce appropriate Th1 response, as evidenced by the higher rate of viral infections in these patients. Also, as African Americans seem to be disproportionately affected by COVID-19, understanding if there are ethnic differences in mounting COVID-19 responses in the setting of systemic and biologic treatments (i.e dupilumab), is crucial. This study is in scope to the parent award (RFA-AI-19-015), as we are an ADRN clinical site, and this study focuses on understanding COVID-19 in AD patients with different phenotypes based on ethnicity, treatment and severity. We are requesting an administrative supplement under NOT-AI-20-031 to support this project. The hypothesis of this study is that Th2 blockade preferentially promotes a Th1-skewed anti-viral immune response, leading to decreased or asymptomatic clinical severity with SARS-CoV-2/COVID-19 infection. The aims of this study are: 1) To evaluate the incidence and severity of COVID-19 among patients currently treated for AD dupilumab (as compared to a group of AD patients treated with broad oral immune suppressants); 2) To evaluate whether African American patients with AD on dupilumab have milder symptoms in the setting of COVID-19 compared to African American patients treated with other immune suppressants, and whether there are differences in mounting viral responses between patients of different ethnicities treated with dupilumab; 3) To evaluate and characterize immune responses in AD patients with reported symptoms of COVID-19 on dupilumab and other broad immunosuppressants using proteomic and transcriptomic approaches.

项目摘要/摘要 面对大流行的巨大努力，以了解抗病毒免疫反应 COVID-19/SARS-COV-2。理解中度至重度特应性皮炎的免疫反应至关重要 （AD）正在接受全身性免疫调节药物并感染COVID-19的患者。广告 患者（患有和没有哮喘）的病毒感染风险增加。表征对 AD患者的Covid-19感染可能指导这些患者的治疗方式，并告知是否是否 在无症状或有症状感染的情况下，需要修改或停止治疗。 尽管一些研究表明，Th2细胞因子（除其他细胞因子）在严重病中升高 迄今为止尚未发表任何努力 评估Th2炎症在19009例患者中的症状和结局严重程度中的作用。 此外，接受Th2封锁的患者中，199症状的发生率和严重程度 特应性皮炎与杜皮鲁马布（Dupilumab 亚基，尚未评估。长期以来一直认为，异常升高的Th2轴极化 AD和哮喘患者的设置可能会对免疫系统诱导的能力产生负面影响 适当的Th1反应，这些患者的病毒感染率较高，证明了这一点。另外，作为非洲人 美国人似乎受到199的影响不成比例，了解是否存在种族差异 在安装互联-19的响应中，在系统性和生物学处理的情况下（即dupilumab）至关重要。 这项研究符合父母奖（RFA-AI-19-015）的范围，因为我们是ADRN临床站点，本研究 专注于理解基于种族，治疗不同表型的AD患者的Covid-19 和严重性。我们要求根据非AI-20-031进行管理补充，以支持该项目。 这项研究的假设是，Th2封锁优先促进了Th1扭曲的抗病毒 免疫反应，导致SARS-COV-2/COVID-19导致或无症状的临床严重程度降低或无症状的临床严重程度 感染。这项研究的目的是：1）评估患者Covid-19的发病率和严重程度 目前接受了AD Dupilumab治疗（与接受广泛口服免疫治疗的一组AD患者相比 抑制剂）； 2）评估非裔美国人AD上的dupilumab患者是否患有较轻的症状 与接受其他免疫抑制剂治疗的非裔美国人患者相比，在Covid-19的环境中 以及在接受治疗的不同种族患者之间安装病毒反应的安装反应差异是否存在差异 与Dupilumab； 3）评估和表征与报告症状的AD患者的免疫反应 使用蛋白质组学和转录组学上的杜皮鲁姆单抗和其他广泛的免疫抑制剂上的covid-19 方法。