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

Great efforts are made in the face of the pandemic to understand anti-viral immune responses toCOVID-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. ADpatients(with and without asthma), are at increased risk for viral infections. Characterizing responses toCOVID-19 infection in AD patients may guide the way these patients are treated, and inform on whethertreatments 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 illpatients admitted to ICUs with pneumonia secondary to COVID-19, no efforts have been published thus farevaluating 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 foratopic dermatitis with dupilumab, a monoclonal antibody targeting the IL-4/IL-13 signaling IL-4R receptor alphasubunit, has not been evaluated. It has long been believed that abnormally elevated Th2-axis polarization inthe setting of AD and asthma patients may negatively impact the ability of the immune system to induceappropriate Th1 response, as evidenced by the higher rate of viral infections in these patients. Also, as AfricanAmericans seem to be disproportionately affected by COVID-19, understanding if there are ethnic differencesin 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 studyfocuses on understanding COVID-19 in AD patients with different phenotypes based on ethnicity, treatmentand 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-viralimmune response, leading to decreased or asymptomatic clinical severity with SARS-CoV-2/COVID-19infection. The aims of this study are: 1) To evaluate the incidence and severity of COVID-19 among patientscurrently treated for AD dupilumab (as compared to a group of AD patients treated with broad oral immunesuppressants); 2) To evaluate whether African American patients with AD on dupilumab have milder symptomsin 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 treatedwith dupilumab; 3) To evaluate and characterize immune responses in AD patients with reported symptoms ofCOVID-19 on dupilumab and other broad immunosuppressants using proteomic and transcriptomicapproaches.