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

项目总结/摘要 面对大流行，人们做出了巨大努力，以了解抗病毒免疫反应， COVID-19/SARS-CoV-2。了解中重度特应性皮炎的免疫反应是至关重要的 (AD)正在接受全身免疫调节药物治疗并感染COVID-19的患者。AD 患者（有和没有哮喘），病毒感染的风险增加。对以下问题的反应进行表征 AD患者的COVID-19感染可能会指导这些患者的治疗方式，并告知是否 在出现无症状或有症状感染的情况下，需要调整或停止治疗。 尽管一些研究已经表明，Th 2细胞因子（在其他细胞因子中）在严重疾病患者中升高，但在严重疾病患者中，Th 2细胞因子（在其他细胞因子中）在严重疾病患者中升高。 因COVID-19继发性肺炎而入住ICU的患者，迄今为止尚未公布任何努力 评估Th 2炎症在COVID-19患者症状严重程度和结局中的作用。 此外，接受Th 2阻断治疗的患者中COVID-19症状的发生率和严重程度 dupilumab（一种靶向IL-4/IL-13信号传导IL-4 R受体α的单克隆抗体）治疗特应性皮炎 子单元尚未评估。长期以来，人们一直认为，异常升高的Th 2轴极化与肿瘤的发生有关。 AD和哮喘患者的情况可能会对免疫系统诱导 适当的Th 1应答，如这些患者中较高的病毒感染率所证明的。作为非洲 美国人似乎不成比例地受到COVID-19的影响，了解是否存在种族差异 在系统性和生物治疗（即dupilumab）的背景下增加COVID-19反应至关重要。 本研究在母合同（RFA-AI-19-015）的范围内，因为我们是ADRN临床研究中心，本研究 专注于了解基于种族、治疗、年龄和性别的不同表型AD患者中的COVID-19 和严重性我们正在根据NOT-AI-20-031申请行政补充，以支持该项目。 本研究的假设是，Th 2阻断优先促进Th 1偏斜的抗病毒药物， 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 目前接受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）评价接受dupilumab治疗的非裔美国AD患者是否具有较轻的症状 与接受其他免疫抑制剂治疗的非裔美国人患者相比， 以及不同种族的患者在病毒应答方面是否存在差异 3）评价和表征报告有以下症状的AD患者的免疫应答： 使用蛋白质组学和转录组学研究COVID-19对dupilumab和其他广泛免疫抑制剂的影响 接近。

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.