Large cohort study shows increased risk of developing atopic dermatitis after COVID-19 disease.

To the Editor, Atopic dermatitis (AD) is a frequent, chronic inflammatory disease constituting significant burden to patients, their families and healthcare systems.1 The pathophysiology is multifactorial involving genetic predisposition, epidermal dysfunction, and cutaneous inflammation.2 Systemic infections trigger AD flares and are related to the manifestation of new-onset AD.1 Following the acute phase of a SARS-CoV-2 infection, some people develop long-lasting symptoms, known as post- or long-COVID.3 Different incident diseases are associated with prior COVID-19 disease, including cardiovascular and respiratory diseases, mental health problems, fatigue, and autoimmune diseases.4, 5 Due to the role of viral infections in the pathophysiology of AD, we hypothesized that the risk of new-onset AD is increased in individuals with previous SARS-CoV-2 infection. To test this, we undertook a large matched cohort study based on German routine healthcare data covering inpatient and outpatient care, diagnoses, prescriptions and demographic data. Patients with polymerase chain reaction (PCR)-confirmed COVID-19 infection in the year 2020 were matched 1:3 by age, sex, previous occurrence of an autoimmune disease and comorbidity propensity score to control subjects without COVID-19-infection and followed up to 15 months through June 2021. Patients with prevalent AD in the four quarters (one inpatient diagnosis or two outpatient diagnoses in two different quarters with ICD-10: L20 or L30 for adults) before the initial SARS-CoV-2 infection or their assigned index date were excluded. Following the NICE guidelines on long-COVID,3 we defined the post-COVID-19-phase starting 3 months after the assigned index date. Primary outcome was new-onset AD. Patients were considered as having new-onset AD, if they received at least two physician documented diagnoses of AD (ICD-10: L20 or L30 for adults), no more than two quarters apart or an inpatient diagnosis in the post-COVID period. Additionally, we requested at least one prescription of topical or systemic treatment approved for AD (Table S1). We calculated incidence rates (IR) per 1000 person-years for the entire study population and predefined subgroups using Poisson models to estimate the IR-ratios (IRR) for the development of AD as a function of a prior diagnosis of COVID-19.5 Because of the non-interventional nature of routine healthcare data, no consent to participate was collected. This waiver for informed consent was confirmed by ethics committee of the Faculty of Medicine Carl Gustav Carus at the TU Dresden (BO-EK [COVID]-482,102,021). In total, 641,704 COVID-19-patients, and 1,907,992 matched control cases without COVID-19 were included (Figure S1). 23,740 patients in the COVID-19-group and 111,818 cases in the control cohort were excluded because of prior AD. The IR of AD 3 to 15 months after the assigned index date was 7.35 (95%-CI 7.11–7.59) per 1000 person-years in the COVID-19 group and 5.53 (95% CI: 5.32–5.74) in the control group. The largest risk difference was observed among those under 18 years of age. Thus, patients with prior COVID-19 infection had a 33% increased risk of developing AD compared to controls (IRR 1.33; 95%-CI 1.26–1.40). The risk for new-onset AD was significantly increased in both sex groups, medication groups and all age groups. However, the confidence intervals of the relative risks overlapped between these groups. (Table 1, Figure 1). In summary, our study shows consistent and significantly increased new-onset of AD in patients with previous SARS-CoV-2 infection. Limitations of the presented study include its observational nature so that causal conclusions can only be drawn with caution. A major strength is the large sample size and the robustness of the findings in several analyzed subgroups. This new evidence strengthens previous studies that suggested a relevant pathophysiological role of viral infections in AD.6 Future research is necessary to further investigate the role of the COVID-19 pandemic on the global burden of AD. Conception: all authors Methodology: JS, FT, FE, DW, MB, FL, SM, MS, CS. Data analysis: FT, FE. Writing of draft paper: JS, BK, SA. Revision and approval of final paper: all authors. The authors thank the participating statutory health insurer for the opportunity to use their data for research. Open Access funding was made possible by Projekt DEAL. This work was supported by a research grant from the German Ministry of Health (Grant Number ZMI1-2521NIK705). Unrelated to this study, JS reports grants for investigator-initiated research from the German GBA, the BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings for Sanofi, Lilly, and ALK. MB reports payment for data analysis which is presented in this paper from DAK-Gesundheit. Unrelated to this study, MB reports grants from German GBA, Pfizer and Sanofi Pasteur and consulting fees from Janssen-Cilag. He participated in an advisory board for GSK. SA has received speaking and/or consulting fees and is involved in clinical trials for Novartis, Sanofi, Beiersdorf, UCB, Amgen, LEO Pharma, Tekeda, Lilly, Boehringer Ingelheim, and AbbVie. The other authors declare that they have no competing interest. The raw data used in this study cannot be made available in the manuscript, the supplemental files, or in a public repository due to German data protection laws (Bundesdatenschutzgesetz). The aggregated data is stored on a secure drive at ZEGV. Table S1: Medication atopic dermatitis. Figure S1: Flowchart for the selection of the COVID-19 and control groups. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.