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.

Public Health Relevance

This research project has the potential to directly impact the medical care of tens of thousands of patients in the United States with atopic dermatitis on systemic medications in the setting of the COVID-19 pandemic, reducing morbidity and mortality, particularly in populations disproportionately affected, such as African Americans. Furthermore, better understanding of differential immune responses mounted to COVID-19 may provide further insight into immune responses to COVID-19, and offer a basis for evaluating additional therapeutic approaches for COVID-19 and other infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AI152036-01S1
Application #
10159603
Study Section
Program Officer
Minnicozzi, Michael
Project Start
2020-06-04
Project End
2022-03-31
Budget Start
2020-06-04
Budget End
2021-03-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Dermatology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029