Previous studies suggest that allergic diseases may be a protective factor in SARS-CoV-2 infection. However, data regarding the impact of dupilumab, a widely used immunomodulatory medication, on COVID-19 in an allergic population are very limited. To investigate the incidence and severity of COVID-19 among moderate-to-severe atopic dermatitis (AD) patients treated with dupilumab, a retrospective cross-sectional survey was conducted among patients with moderate-to-severe AD who presented at the Department of Allergy of Tongji Hospital from 15 January 2023 to 31 January 2023. Healthy individuals matched for gender and age were also enrolled as a control. All subjects were asked about their demographic characteristics, past medical history, COVID-19 vaccination history, and medications, as well as the presence and duration of individual COVID-19-related symptoms. A total of 159 moderate-to-severe AD patients and 198 healthy individuals were enrolled in the study. Among the AD patients, 97 patients were treated with dupilumab, and 62 patients did not receive any biologicals or systemic treatments (topical treatment group). The proportions of people who were not infected with COVID in the dupilumab treatment group, topical treatment group and healthy control group were 10.31%, 9.68% and 19.19%, respectively (p = 0.057). There was no significant difference in COVID-19-related symptom scores among all groups (p = 0.059). The hospitalization rates were 3.58% in the topical treatment group and 1.25% in the healthy control group, and no patient was hospitalized in the dupilumab treatment group (p = 0.163). Compared with healthy control group and topical treatment group, the dupilumab treatment group had the shortest COVID-19-associated disease duration (dupilumab treatment group, 4.15 ± 2.85 d vs. topical treatment group, 5.43 ± 3.15 d vs. healthy control group, 6.09 ± 4.29 d; p = 0.001). Among the AD patients treated with dupilumab for different times, there was no appreciable difference (<0.5 year group, 5 ± 3.62 d vs. 0.5-1 year group, 4.84 ± 2.58 d vs. >1 year group, 2.8 ± 1.32 d; p = 0.183). Dupilumab treatment shortened the duration of COVID-19 in patients with moderate-to-severe AD. AD patients can continue their dupilumab treatment during the COVID-19 pandemic.