key: cord-0927633-rp6beyl3 authors: Ungar, Benjamin; Lavin, Leore; Golant, Alexandra K.; Gontzes, Alyssa; David, Eden; Estrada, Yeriel D.; Singer, Giselle K.; Pavel, Ana B.; Guttman-Yassky, Emma title: The impact of dupilumab treatment on SARS-CoV-2/COVID-19 antibody responses in atopic dermatitis patients date: 2022-03-26 journal: Ann Allergy Asthma Immunol DOI: 10.1016/j.anai.2022.03.019 sha: dcd02d0cce94263176236bf8c5bd5d2938a89de6 doc_id: 927633 cord_uid: rp6beyl3 nan Immunomodulatory therapies are commonly used to treat patients with moderate-to-severe atopic dermatitis (AD). Thus, it is critical to understand their effects on COVID-19 outcomes. We recently showed that AD patients on dupilumab were more likely to be asymptomatic or have milder COVID-19 symptoms. 1 However, the impact of dupilumab and systemic immunosuppressants on SARS-CoV-2/COVID-19 antibody levels in AD patients remains unknown. We thus evaluated IgG antibody levels in unvaccinated patients with COVID-19 infection and after mRNA vaccination. As part of a prospective registry related to COVID-19 in the Department of Dermatology at the Icahn School of Medicine at Mount Sinai, we collected serum samples from patients prior to vaccination and after mRNA vaccination, between June 8, 2020 and October 14, 2021. Patients were enrolled under institutional review board-approved consent, and the study was conducted according to the Declaration of Helsinki. Inclusion criteria included being older than 12 years of age with a diagnosis of moderate-to-severe AD, defined as currently or previously being on systemic therapy (including dupilumab, phototherapy, or oral immunomodulatory medications), or as candidates for systemic therapy. Based reported COVID-19-related symptoms, each patient was given a COVID-19 symptom severity score from 0 to 2: 0: "asymptomatic"; 1: "mild disease" (no fever, no dyspnea, resolving in <7 days, resembling a common cold); 2: "moderate disease" (some fever and/or cough, or other lower respiratory symptoms, resolving at home in 7-14 days). As our aim was to compare the effects of dupilumab treatment on antibody responses, we only included samples from patients on dupilumab for at least 2 months at the time sample collection (to ensure enough time and treatment had passed to allow effects of dupilumab to manifest). Patients with positive IgG antibodies in the absence of vaccination were defined as COVID-19-infected. SARS-CoV-2 IgG antibody levels were measured using the Mount Sinai Laboratory COVID-19 Enzyme-Linked ImmunoSorbent Assay (ELISA) IgG Antibody Test, which received FDA Emergency Use Authorization (https://www.fda.gov/media/137029/download), but used for research purposes in this study. Antibody levels were categorized into 4 groups based on the Mount Sinai Laboratory predefined levels: negative (< 5AU/mL), weak (5 -15 AU/mL), moderate (16-39 AU/mL) and strong (≥40 AU/mL). Three treatment groups were compared: 1) "Limited": topical therapy or no active treatment; 2) Systemics: broad-acting treatments (JAK-inhibitors, prednisone, phototherapy), and 3) Dupilumab. Antibody group proportions were compared using two-sided Fisher test, and log 10 antibody level comparison were performed using multivariate linear regression models. No significant differences were observed in terms of age, gender, or race between the 3 treatment groups prior to vaccination (age: p=0.07; gender: p=0.10; race p=0.18) or after vaccination (age: p=0.26; gender: p=0.08; race: p=0.45), Among the 54 COVID-19-positive samples pre-vaccination, decreased symptom severity was associated with lower IgG antibody levels across all treatments, consistent with studies associating more severe COVID-19 with greater SARS-CoV-2 IgG antibody levels. [1] [2] [3] [4] [5] To assess if lower antibody levels were due to treatment-based modulation of antibody production or from differential responses to SARS-CoV-2 virus itself, we then assessed antibody levels after mRNA vaccination. Overall, we found similar rate decreases in antibody levels over time between treatment groups ( Figure 1) . Correspondingly, no differences were observed between groups between antibody level groups (weak/moderate/strong). Furthermore, using a linear regression model adjusted for age and time after vaccination, we detected no significant differences in antibody concentrations between any treatment groups (p>0.18). Overall, this study found that patients had significantly lower antibody levels after COVID-19 infection when treated with dupilumab vs. systemic therapies, as well as lower levels (approaching significance) compared with patients receiving limited/no therapy, paralleling our previous finding that dupilumab-treated patients were more likely to have milder symptoms COVID-19 symptoms compared to patients on broad-acting treatments and also those receiving limited/no treatment. 1 However, there were no differences in antibody levels between treatment groups after mRNA vaccination. This suggests that dupilumab does not impair antibody responses, but rather, reduces COVID-19 symptom severity and downstream IgG levels. Limitations of this study include unknown COVID-19 infection dates (often due to lack of symptoms and therefore testing), the smaller number of Systemic patients that tested positive to COVID-19, matching our practice prescribing tendencies, and the absence of a control group without AD. Further studies to characterize T-cell components of COVID-19 immune responses with different immunomodulatory treatments are needed. Taken together with our previous publication showing ameliorated COVID-19 symptoms with dupilumab treatment in AD, these results provide reassurance that specific Th2-targeting in AD patients does not affect antibody levels after mRNA vaccination and supports continuing dupilumab treatment during the COVID-19 pandemic irrespective of vaccination status. Symptoms Are Attenuated in Moderate-to-Severe Atopic Dermatitis Patients Treated with Dupilumab Humoral immune mechanisms involved in protective and pathological immunity during COVID-19 Cross-reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study High neutralizing antibody titer in intensive care unit patients with COVID-19 Antibody Responses to SARS CoV-2 in Patients With Novel Coronavirus Disease We thank the Mount Sinai Biorepository & Pathology Core for providing support in antibody sample processing.