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: 10159603
• 负责人: Emma Guttman
• 金额: $ 24.49万
• 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/10159603
• 关键词: 2019-nCoV; Administrative Supplement; Affect; African American; Antiviral Agents; Asthma; Atopic Dermatitis; Award; Biological; Biological Response Modifier Therapy; Blood; COVID-19; COVID-19 pandemic; Caring; Clinical; Cyclosporine; Dermatology; Ethnic Origin; Extrinsic asthma; Immune; Immune response; Immune system; Immunosuppressive Agents; Incidence; Infection; Inflammation; Interleukin-13; Interleukin-4; Medical; Monoclonal Antibodies; Morbidity - disease rate; Oral; Outcome; Parents; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Pneumonia; Population; Proteomics; Publishing; Reporting; Research; Research Project Grants; Risk; Role; Secondary to; Severities; Signal Transduction; Site; Symptoms; Therapeutic; United States; Viral; Virus Diseases; asthmatic patient; base; clinical center; clinical research site; cytokine; disease phenotype; ethnic difference; inhibitor/antagonist; insight; mortality; pandemic disease; receptor; response; transcriptomics

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.

项目总结/文摘