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.

项目概要/摘要 面对大流行，人们付出了巨大努力来了解抗病毒免疫反应 COVID-19/SARS-CoV-2。了解中度至重度特应性皮炎的免疫反应至关重要 (AD) 正在接受全身免疫调节药物并感染了 COVID-19 的患者。广告 患者（患有或不患有哮喘）病毒感染的风险增加。表征响应 AD 患者中的 COVID-19 感染可能会指导这些患者的治疗方式，并告知是否 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（以及其他细胞因子）在重症患者中升高 因 COVID-19 继发肺炎入住 ICU 的患者，迄今为止尚未发表任何努力 评估 Th2 炎症在 COVID-19 患者症状严重程度和结果中的作用。 此外，接受 Th2 阻断治疗的患者中 COVID-19 症状的发生率和严重程度 使用 dupilumab 治疗特应性皮炎，dupilumab 是一种针对 IL-4/IL-13 信号传导 IL-4R 受体 α 的单克隆抗体 亚单位，尚未评估。长期以来，人们一直认为，异常升高的 Th2 轴极化 AD 和哮喘患者的环境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就证明了这一点。另外，作为非洲人 美国人似乎受到 COVID-19 的影响尤为严重，了解是否存在种族差异 在全身和生物治疗（即 dupilumab）的背景下提高 COVID-19 反应至关重要。 这项研究属于家长奖 (RFA-AI-19-015) 的范围，因为我们是 ADRN 临床中心，并且这项研究 重点了解基于种族、治疗的不同表型 AD 患者中的 COVID-19 和严重程度。我们正在请求 NOT-AI-20-031 下的行政补充以支持该项目。 本研究的假设是 Th2 阻断优先促进 Th1 偏向的抗病毒作用 免疫反应，导致 SARS-CoV-2/COVID-19 临床严重程度降低或无症状 感染。本研究的目的是：1) 评估患者中 COVID-19 的发病率和严重程度 目前正在接受 AD dupilumab 治疗（与一组接受广泛口服免疫治疗的 AD 患者相比） 抑制剂）； 2) 评估使用dupilumab治疗的非裔美国AD患者是否有较轻的症状 与接受其他免疫抑制剂治疗的非裔美国患者相比，在 COVID-19 的情况下， 不同种族接受治疗的患者之间的病毒反应是否存在差异 与杜匹鲁单抗一起使用； 3) 评估和表征具有报告症状的 AD 患者的免疫反应 使用蛋白质组学和转录组学研究 dupilumab 和其他广泛免疫抑制剂的 COVID-19 接近。