13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Received: 2 October 2020 | Revised: 9 November 2020 | Accepted: 16 November 2020 DOI: 10.1111/all.14687 ORIGINAL ARTICLE Atopic Dermatitis, Urticaria and Skin Disease The global impact of the COVID-19 pandemic on the management and course of chronic urticaria Emek Kocatürk1 | Andaç Salman2 | Ivan Cherrez-Ojeda3 | Paulo Ricardo Criado4,5,6 | Jonny Peter7 | Elif Comert-Ozer2 | Mohamed Abuzakouk8 | Rosana Câmara Agondi9 | Mona Al-Ahmad10 | Sabine Altrichter11 | Rand Arnaout12 | Luisa Karla Arruda13 | 14 15 16 17 Riccardo Asero | Andrea Bauer | Moshe Ben-Shoshan | Jonathan A. Bernstein | Mojca Bizjak18 | Isabelle Boccon-Gibod19 | Hanna Bonnekoh20,21 | 19 22 23 Laurence Bouillet | Zenon Brzoza | Paula Busse | Regis A Campos24,25 | Emily Carne26 | Niall Conlon27 | Roberta F. Criado28 | Eduardo M. de Souza Lima29 | Semra Demir30 | Joachim Dissemond31 | Sibel Doğan Günaydın32 | Irina Dorofeeva33 | Luis Felipe Ensina34 | Ragıp Ertaş35 | Silvia Mariel Ferrucci36 | Ignasi Figueras-Nart37 | Daria Fomina38,39 | Sylvie M Franken40 | Atsushi Fukunaga41 | Ana M. Giménez-Arnau42 | Kiran Godse43 | Margarida Gonçalo44 | Maia Gotua45 | Clive Grattan46 | Carole Guillet47 | Naoko Inomata48 | Thilo Jakob49 | Gul Karakaya50 | Alicja Kasperska-Zając51 | Constance H Katelaris52 | Mitja Košnik18 | 53 54 55 Dorota Krasowska | Kanokvalai Kulthanan | M. Sendhil Kumaran | Claudia Lang47 | José Ignacio Larco-Sousa56 | Elisavet Lazaridou57 | Tabi Anika Leslie58 | Undine Lippert59 | Oscar Calderón llosa60 | Michael Makris61 | Alexander Marsland62 | Iris V. Medina63 | Raisa Meshkova64 | Esther Bastos Palitot65 | Claudio A.S. Parisi66 | Julia Pickert67 | German D. Ramon68 | Mónica Rodríguez-Gonzalez69 | Nelson Rosario70 | Michael Rudenko71 | Krzysztof Rutkowski72 | Jorge Sánchez73 | Sibylle Schliemann74 | Bulent Enis Sekerel75 | Faradiba S. Serpa76 | Esther Serra-Baldrich77 | Zhiqiang Song78 | Angèle Soria79 | Maria Staevska80 | Petra Staubach81 | Anna Tagka82 | Shunsuke Takahagi83 | Simon Francis Thomsen84 | Regina Treudler85 | Zahava Vadasz86 | Solange Oliveira Rodrigues Valle87 | Martijn B.A. Van Doorn88 | Christian Vestergaard89 | Nicola Wagner90 | Dahu Wang91 | Liangchun Wang92 | Bettina Wedi93 | Paraskevi Xepapadaki94 | Esra Yücel95 | Anna Zalewska-Janowska96 | Zuotao Zhao97 | 21 98 Torsten Zuberbier | Marcus Maurer 1 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Koç University School of Medicine, Istanbul, Turkey 2 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Marmara University School of Medicine, Istanbul, Turkey 3 Urticaria Center of Reference and Excellence (UCARE), School of Medicine, Universidad de Especialidades Espíritu Santo, Samborondón, Ecuador and RespiraLab, Research, Guayaquil, Ecuador This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd 816 |  wileyonlinelibrary.com/journal/all Allergy. 2021;76:816–830. | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License KOCATÜRK et al. 817 4 Urticaria Center of Reference and Excellence (UCARE), Faculdade de Medicina do ABC, Santo André, Brazil 5 Alergoskin Alergia e Dermatologia SS ltda, Santo André, Brazil 6 UCARE Center, São Paulo, Brazil 7 Urticaria Center of Reference and Excellence (UCARE), Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, 7925, South Africa 8 Urticaria Center of Reference and Excellence (UCARE), Cleveland Clinic Abu Dhabi, UAE 9 Urticaria Center of Reference and Excellence (UCARE), University of São Paulo, São Paulo, Brazil 10 Urticaria Center of Reference and Excellence (UCARE), Microbiology Department, Faculty of Medicine, Kuwait University, Safat, Kuwait 11 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany 12 Urticaria Center of Reference and Excellence (UCARE), King Faisal Specialist Hospital & Research Center, Al Faisal University, Riyadh, Saudi Arabia 13 Urticaria Center of Reference and Excellence (UCARE), Preto Medical School, University of São Paulo, São Paulo, Brazil 14 Urticaria Center of Reference and Excellence (UCARE), Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy 15 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, University Allergy Center, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany 16 Urticaria Center of Reference and Excellence (UCARE), Division of Allergy, Immunology and Dermatology, Department of Pediatrics, McGill University Health Center, Montreal, QC, Canada 17 Urticaria Center of Reference and Excellence (UCARE), University of Cincinnati College of Medicine, Division of Immunology, Rheumatology and Allergy, Cincinnati, USA 18 Urticaria Center of Reference and Excellence (UCARE), Division of Allergy, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 19 Urticaria Center of Reference and Excellence (UCARE), Clinical Immunology/Internal Medicine Department, National Reference Center for Angioedema, Grenoble University Hospital, Grenoble, France 20 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany 21 Autoinflammation Reference Center Charité (ARC2), Charité - Universitätsmedizin Berlin, Berlin, Germany 22 Urticaria Center of Reference and Excellence (UCARE), Department of Internal Medicine with Division of Allergology, Institute of Medical Sciences, University of Opole, Opole, Poland 23 Urticaria Center of Reference and Excellence (UCARE), Division of Clinical Immunology and Allergy, Icahn School at Mount Sinai, New York, NY, USA 24 Urticaria Center of Reference and Excellence (UCARE), Universidade Federal da Bahia, Salvador, Brazil 25 Serviço de Imunologia, Hospital das Clínicas Professor Edgard Santos, Salvador, Brazil 26 Urticaria Center of Reference and Excellence (UCARE), University Hospital of Wales, Cardiff, UK 27 Urticaria Center of Reference and Excellence (UCARE), Department of Immunology, St James’s Hospital and Trinity College, Dublin, Ireland 28 Urticaria Center of Reference and Excellence (UCARE), Faculdade de Medicina do ABC (FMABC), Santo André, Brazil 29 Urticaria Center of Reference and Excellence, (UCARE), Faculdade de Ciências, Médicas e da Saúde de Juiz de Fora (SUPREMA), Hospital Maternidade Therezinha de Jesus, Minas Gerais, Brazil 30 Urticaria Center of Reference and Excellence (UCARE), Division of Allergy, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey 31 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Venereology and Allergology, University of Essen, Essen, Germany 32 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey 33 Urticaria Center of Reference and Excellence (UCARE), Department of Allergy and Immunotherapy, Institute of Immunology, FMBA of Russia, Moscow, Russia 34 Urticaria Center of Reference and Excellence (UCARE), Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil 35 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Kayseri City Education and Research Hospital, Kayseri, Turkey 36 Urticaria Center of Reference and Excellence (UCARE), Ambulatorio di Dermatologia Allergologica e Professionale, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy 37 Urticaria Center of Reference and Excellence (UCARE), The Dermatology Department of the Hospital de Bellvitge, Universitat de Barcelona, Barcelona, Spain 38 Urticaria Center of Reference and Excellence (UCARE), Center of Allergy and Immunology, Moscow Ministry of Healthcare, Moscow, Russia 39 Department of Allergology and Clinical Immunology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia 40 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Amsterdam UMC, Amsterdam, The Netherlands 41 Urticaria Center of Reference and Excellence (UCARE), Division of Dermatology, Kobe University, Graduate School of Medicine, Kobe, Japan 42 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Hospital del Mar, IMIM, Universitat Autònoma, Barcelona, Spain 43 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, D Y. Patil University School of Medicine, Mumbai, India 44 Urticaria Center of Reference and Excellence (UCARE), Centro Hospitalar Universitário Coimbra and Faculty of Medicine, University of Coimbra, Clinica de Dermatologia, Coimbra, Portugal 45 Urticaria Center of Reference and Excellence (UCARE, Center of Allergy and Immunology, Tbilsi, Georgia | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 818 KOCATÜRK et al. 46 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Guys & St Thomas' Hospital, London, UK 47 Urticaria Center of Reference and Excellence (UCARE), Allergy Unit, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland 48 Urticaria Center of Reference and Excellence (UCARE), Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan 49 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Allergy, University Medical Center Giessen (UKGM, Justus-Liebig- University Giessen, Giessen, Germany 50 Urticaria Center of Reference and Excellence (UCARE), School of Medicine, Department of Chest Diseases, Adult Allergy Unit, Hacettepe University, Sihhiye Ankara, Turkey 51 Urticaria Center of Reference and Excellence (UCARE), European Center for Diagnosis and Treatment of Urticaria, Medical University of Silesia, Zabrze, Poland 52 Urticaria Center of Reference and Excellence (UCARE), Immunology & Allergy Unit, Department of Medicine, Campbelltown Hospital, Campbelltown, NSW, Australia 53 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland 54 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 55 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 56 Urticaria Center of Reference and Excellence (UCARE), Clinica San Felipe, Lima, Peru 57 Urticaria Center of Reference and Excellence (UCARE), Second department of Dermatology and Venereology, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece 58 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Royal Free Hospital, London, UK 59 Urticaria Center of Reference and Excellence (UCARE, Department of Dermatology, Medical Center of University Goettingen, Venerology und Allergology, Goettingen, Germany 60 Urticaria Center of Reference and Excellence (UCARE), Department of Allergy, SANNA el Golf, San Isidro, Lima 61 Urticaria Center of Reference and Excellence (UCARE), Second Department of Dermatology and Venereology, National and Kapodistrian University of Athens, University General Hospital “Attikon”, Athens, Greece 62 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, The Urticaria Clinic, Salford Royal Foundation Trust, University of Manchester, Manchester, UK 63 Urticaria Center of Reference and Excellence (UCARE), Allergy and Clinical Immunology Department, Centro Médico Vitae, de Julio, Argentina 64 Urticaria Center of Reference and Excellence (UCARE), Department of Clinical Immunology and Allergology, Smolensk State Medical University, Smolensk, Russia 65 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Hospital Universitário Lauro Wanderley, João Pessoa, PB, Brazil 66 Urticaria Center of Reference and Excellence (UCARE), Adults and Pediatrics Allergy Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina 67 Urticaria Center of Reference and Excellence (UCARE), Clinical & Experimental Allergology, Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany 68 Urticaria Center of Reference and Excellence (UCARE), Instituto de Alergia e Inmunologia del Sur, Buenos Aires, Argentina 69 Urticaria Center of Reference and Excellence (UCARE), Department of Allergy, Hospital Español de México, Mexico City, Mexico 70 Urticaria Center of Reference and Excellence (UCARE), Federal University of Parana, Rua General Carneiro, Curitiba, Brazil 71 Urticaria Center of Reference and Excellence (UCARE), London Allergy and Immunology Centre, London, UK 72 Urticaria Center of Reference and Excellence (UCARE), Department of Allergy, Guy's and St Thomas’ Hospital NHS Foundation Trust, London, UK 73 Urticaria Center of Reference and Excellence (UCARE), Department of Pediatrics, Graduate Program on Allergology, University of Antioquia, Medellín, Colombia 74 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, University Hospital Jena, Germany 75 Urticaria Center of Reference and Excellence (UCARE), Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey 76 Urticaria Center of Reference and Excellence (UCARE), Hospital Santa Casa de Misericórdia de Vitória, Espírito Santo, Brazil 77 Urticaria Center of Reference and Excellence (UCARE), Dermatology Department, Hospital Sant Pau, Barcelona, Spain 78 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, China 79 Urticaria Center of Reference and Excellence (UCARE), Service de Dermatologie et Allergologie, Hopital Tenon, APHP, Université, Paris, Sorbonne, France 80 Urticaria Center of Reference and Excellence (UCARE), Department of Allergy, Sofia Medical University, Sofia, Bulgaria 81 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, University Medical Center, Mainz, Germany 82 Urticaria Center of Reference and Excellence (UCARE), First Department of Dermatology and Venereology, National and Kapodistrian University of Athens, "A. Syggros" Hospital, Referral Center of Occupational Dermatological Diseases, Athens, Greece 83 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan 84 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark 85 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Venerology and Allergology and Leipzig Interdisciplinary Center of | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License KOCATÜRK et al. 819 Allergology Comprehensive Allergy Center, UMC Leipzig, Leipzig, Germany 86 Urticaria Center of Reference and Excellence (UCARE), Division of Allergy and Clinical Immunology, Bnai-Zion Medical Center, Technion Faculty of Medicine, Haifa, Israel 87 Urticaria Center of Reference and Excellence (UCARE), Federal University of Rio de Janeiro, Department of Internal Medicine, Immunology Service, Rio de Janeiro, Brazil 88 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands 89 Urticaria Center of Reference and Excellence (UCARE), Aarhus University Hospital, Aarhus, Denmark 90 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, University of Erlangen, Erlangen, Germany 91 Urticaria Center of Reference and Excellence (UCARE), Dermatovenerological Department, The Second Hospital of HeBei Medical University, Shijiazhuang, HeBei Province, China 92 Urticaria Center of Reference and Excellence (UCARE, Dermatology Department of Sun Yat-sen Memorial Hospital, Guangzhou, China 93 Urticaria Center of Reference and Excellence (UCARE, Department of Dermatology and Allergology, Hannover Medical School, Allergology Division, Hannover, Germany 94 Urticaria Center of Reference and Excellence (UCARE), Department of Allergy, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece 95 Urticaria Center of Reference and Excellence (UCARE), Department of Pediatric Allergy and Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey 96 Urticaria Center of Reference and Excellence (UCARE), Chair of Clinical Immunology and Rheumatology, Department of Psychodermatology, Medical University of Lodz, Lodz, Poland 97 Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venerology, Peking University First Hospital, Beijing Key Laboratory of molecular Diagnosis on Dermatoses and National Clinical Research Center for Skin and Immune Diseases, Beijing, China 98 Urticaria Center of Reference and Excellence (UCARE), Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité – Universitätsmedizin, Berlin, Germany Correspondence Marcus Maurer, Urticaria Center of Abstract Reference and Excellence (UCARE), Introduction: The COVID-19 pandemic dramatically disrupts health care around the Dermatological Allergology, Allergie- Centrum-Charité, Department of globe. The impact of the pandemic on chronic urticaria (CU) and its management are Dermatology and Allergy, Charité largely unknown. – Universitätsmedizin Berlin, Berlin, Germany. Aim: To understand how CU patients are affected by the COVID-19 pandemic; how Email: marcus.maurer@charite.de specialists alter CU patient management; and the course of CU in patients with Emek Kocatürk, Urticaria Center of COVID-19. Reference and Excellence (UCARE), Department of Dermatology, Koç Materials and Methods: Our cross-sectional, international, questionnaire-based, mul- University School of Medicine, Istanbul, ticenter UCARE COVID-CU study assessed the impact of the pandemic on patient Turkey. Email: ekocaturk@ku.edu.tr consultations, remote treatment, changes in medications, and clinical consequences. Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which neg- atively impacted on the care of urticaria patients. The rate of face-to-face consul- tations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, espe- cially the increased use of remote consultations, require careful evaluation. | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 820 KOCATÜRK et al. KEYWORDS chronic urticaria, COVID-19, cyclosporine, omalizumab, pandemic, SARS-CoV-2, treatment, UCARE GR APHIC AL ABSTR ACT The COVID-­19 pandemic severely impairs CU patient care, weekly number of patients decreased by more than 50%, and the rate of face-­ to-­face consultations decreased by 62%. CU does not affect the course of COVID-­19 with only 4% of CU patients having a severe course of COVID-­19, but COVID-­19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-­19. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. Abbreviations: CU, chronic urticarial; COVID-­19, coronavirus disease 2019; UCARE: urticaria centers of reference and excellence. 1 | I NTRO D U C TI O N The COVID-19 pandemic dramatically affects healthcare sys- tems and patient care. Patients with CU and their treating physi- Chronic urticaria (CU) is a common disease with more than 50 million cians are affected by social distancing measures, lockdowns, travel patients affected globally.1 The main effector cells of CU are skin mast restrictions, and changes in management patterns due to the risk cells, often activated by autoimmune mechanisms. This results in the of infection with SARS-CoV-2. CU is a common and often severe release of histamine and other mediators with subsequent sensory disease. A significant number of CU patients are being cared for by nerve activation, vasodilatation, and plasma extravasation as well as expert physicians at hospital-based urticaria centers of reference cell recruitment.2 The first-line treatment of CU is second-generation and excellence (UCAREs).8 The COVID-19 pandemic prompted fre- H1 antihistamines, which provide complete control in less than 50% quent queries to UCAREs from both CU patients and CU treating of the patients, even at up to fourfold doses.3,4 In antihistamine-resis- physicians, especially on the treatment of urticaria with biologics tant patients, treatment with omalizumab and—if this fails—cyclospo- and immunosuppressive treatment. The most common questions of rine is the current guideline-recommended therapy of choice.5 concerns are whether treatment of CU might affect the course of Since the first months of 2020, severe acute respiratory coro- COVID-19, whether the treatments or the disease itself make CU navirus 2 (SARS-CoV-2) has spread rapidly across the globe caus- patients more prone to contract COVID-19 or to result in severe ing the “coronavirus disease 2019” (COVID-19) pandemic, the worst COVID-19, whether COVID-19 aggravates CU, whether the patients global public health crisis since the influenza pandemic more than a can be managed by remote consultations, and whether involvement hundred years ago. As of now, more than 30 million patients have of physicians in COVID-19 care will impair urticaria care. As of now, been diagnosed with COVID-19 around the world, with more than these questions remain unanswered. 900,000 deaths in 188 countries.6 SARS-CoV-2 leads to an upregu- Recently, several scientific societies have issued expert-led prac- lated immune response in the monocytic macrophage system, which tical recommendations on the management of patients with dermato- may produce a severe inflammatory systemic state, hypercoagula- logic or allergic diseases with type 2 inflammation including urticaria tive milieu, and damage in lungs as well as other internal organs, the during the COVID-19 pandemic. These recommendations are based hematological system, gastrointestinal tract, kidneys, and central on expert experience and consensus, rather than evidence from con- nervous system.7 trolled studies. They aim to ensure patient and healthcare worker | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License KOCATÜRK et al. 821 safety, and they provide guidance on the use of treatments including to normal upon remission, similar to chronic spontaneous urticaria, 9-11 biologics and immunosuppressive treatments. For instance, the where high disease activity is linked to basopenia and effective position paper from German Allergologists and European Academy treatment results in normalization of blood basophil numbers.16 of Allergy and Clinical Immunology (EAACI) recommends that treat- These effects may explain why there are several reports of urti- ment of urticaria with omalizumab in patients with mild-to-moder- caria and angioedema associated with COVID-19 infection in the ate COVID-19, or when SARS-CoV-2 infection is suspected, is to literature, and urticaria-like lesions were ranked as the second most be continued if supported by a patient-based risk-benefit analysis common cutaneous manifestation of COVID-19 infection and re- and patient consent. In patients with severe COVID-19, omalizumab ported to be present in 19% of patients in a series from Spain.17 injection interval prolongation or treatment interruption should be Also, COVID-19 can lead to exacerbation of CU.18 How often this considered, taking into account the risk of the possible requirement happens remains unknown. of systemic glucocorticoids.11 If and how these recommendations With the aim of learning from the experience of urticaria specialists are implemented is currently unknown. at UCAREs worldwide, we designed the COVID-CU study to understand The pathogenesis of severe COVID-19 is characterized by ele- how CU patients, their treatment, and course of disease are affected by vated levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 the COVID-19 pandemic. The focus of COVID-CU is to characterize the (IL-6), IL-1β, granulocyte-macrophage colony-stimulating factor changes that the pandemic has brought for the work of UCARE physi- (GM-CSF), and chemokine (C-C-motif) ligand 2 (CCL2),12 many cians who managed their CU patients during the pandemic. of which are produced and released by mast cells. Indeed, SARS- CoV-2 activates mast cells,13 the key effector cells in CU, as well as other immune cells such as basophils, neutrophils, monocytes/ 2 | M ATE R I A L S A N D M E TH O DS macrophages, and natural killer cells, and leads to cytokine storm.14 Mast cells can recognize and respond to viruses through several The COVID-CU study is a cross-sectional, international, multicenter different receptors, including Toll-like receptors, retinoic acid–in- study, in which a 17-item questionnaire was distributed to all mem- ducible gene-I–like receptors, FcεRI, complement, and IL-1 recep- ber centers of the UCARE network (see Appendix-1 for the ques- tors. Engagement of these receptors results in mast cell activation tionnaire) (total 110 centers; https://www.ga2le​n-ucare.com/cente​ and degranulation, the de novo synthesis of eicosanoids as well as rs.html).8 numerous cytokines, chemokines, and growth factors.15 Activation The demographic characteristics of the participating centers are of mast cells in response to viral infection may have protective ef- given in Table 1. fects by helping the immune system or directly fighting the infec- COVID-19 disease severity was defined by using the scale pro- tion. However, worsening of inflammation and severe disease may vided by World Health Organization.19 occur in case of extensive mast cell activation with increased levels of inflammatory cytokine and chemokine release.12 Basophils are also involved in the pathogenesis of COVID-19 and CU. Basophil 2.1 | Questionnaire design numbers are reduced in patients with COVID-19 and levels return The questionnaire was developed by the steering committee mem- TA B L E 1 Demographic characteristics of responding UCARE bers of the COVID-CU study (Emek Kocatürk, Andaç Salman, Jonny physicians (n = 95) Peter, Ivan Cherrez-Ojeda, Paulo Criado, and Marcus Maurer) to Characteristics % (n) query the most prevalent issues that urticaria specialists experience Specialty a Allergy-immunology 62.2 (59) during the COVID-19 pandemic around the world. The focus and se- lection of questions were based on the evolving clinical experience Dermatology 53.7 (51) with the impact of the pandemic on the management of patients and Pediatric allergy 3.2 (3) its impact on UCARE physicians and patients, as well as on patient Internal medicine 2.1 (2) and physician queries. The final version of the survey was approved Practice typea University hospital 81.2 (77) by all COVID-CU steering committee members. The questionnaire Private clinic 24.3 (23) comprised of 17 questions, focused on the impact of the pandemic Public hospital 18 (17) on patient consultations, the implementation of measures for re- Location of UCARE Europe 55.8 (53) mote treatment, changes in the use of medications, and the course of Asia 18.9 (18) COVID-19 in patients with CU. South America 18.9 (18) North America 4.2 (4) 2.2 | Questionnaire implementation Africa 1.1 (1) Australia/Oceania 1.1 (1) The questionnaire was pilot tested by 10 UCAREs before distri- a More than one answer was possible. bution and checked for ease of comprehension. The accuracy and | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 822 KOCATÜRK et al. completeness of the responses were reviewed by the steering com- Windows, Version 20.0. A P value <0.05 was considered as statisti- mittee prior to wider distribution. The survey included a combina- cally significant. tion of fill-in-the-blank and multiple-choice questions. 3 | R E S U LT S 2.3 | Questionnaire distribution 3.1 | The COVID-19 pandemic severely impairs CU Questionnaires were distributed through the UCARE email link to patient care UCARE centers between July 28 and September 1. Three reminders with one-week intervals were sent. During the COVID-19 pandemic, the weekly number of CU pa- tients treated at UCAREs decreased by more than 50% (mean ±SD: 56.6 ± 25.8%; median: 60, range: 0–100). One third of all UCAREs 2.4 | Questionnaire response rate and respondents (n = 33; 34.4%) reported a decrease in patient numbers by more than 75%. Only 5% of UCAREs reported that their patient numbers did Of a total of 110 UCAREs, 95 responded to the questionnaire (re- not change (n = 5; 5.4%; Figure 1a). sponse rate 86.4%). The majority of the respondents were from Reduced patient referrals (n = 57; 61.3%) and urticaria clinic UCAREs at allergy-immunology departments (41.1%), were prac- hours (n = 47; 50.6%) were the major reasons for the decrease in tising at university hospitals (61.1%), and were located in Europe CU patient consultations due to the COVID-19 pandemic (Figure 1b). (55.8%). Characteristics of the respondents are presented in Almost half of the responding UCARE physicians were involved in Table 1. COVID-19 patient care, in inpatient clinics (n = 23; 25.7%), outpatient clinics (16; 17.9%), or intensive care units (n = 3;3.3%) (Table 2). One in four of the affected physicians (n = 14, 23%) agreed or strongly 2.5 | Data analysis agreed that these reassignments negatively impacted on the care of urticaria patients at their UCARE. Quality control of the questionnaire responses was performed. Data were summarized as mean ±standard deviation and median (min.- max.) for continuous variables and frequencies (percentiles) for cate- 3.2 | The COVID-19 pandemic affects the way gorical variables. The Student t test or the Mann-Whitney U test was UCAREs interact with their patients used for independent group comparisons, depending on the distribu- tional properties of the data. The paired-samples t test was used for Face-to-face consultations decreased significantly during the pan- the comparison of means in two related groups. The chi-square test demic, from 90.2% to 34.2% (p < 0.0005). Instead, more consulta- was used for proportions, and its counterpart Fisher's exact test was tions were done via phone calls (35.8%, up from 4.7%; p < 0.0005), used when the data were sparse. Univariate logistic regression analy- WhatsApp (11.5%, up from 3.0%; p < 0.0005); email (7.2%, up from sis was also performed to examine risk factors for different depend- 2.5%; p < 0.0005), and video calls(2.5%, up from 0%; p < 0.007) ent variables. All analyses were performed by IBM SPSS Statistics for (Figure 2). Change in the number of The reason for decrease in weekly CU patients seen weekly number of patients (Before vs During Pandemic) 100% %5 80% %8 %34 60% %18 40% 20% %34 0% No change Patients did not refer to the center F I G U R E 1 (A and B) The changes in Decreased days/hours of consultation the number of CU patients seen weekly Staff involved in COVID-19 care during the pandemic and the reason for Other decrease in number of patients | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License KOCATÜRK et al. 823 TA B L E 2 The involvement of UCARE Responding UCARE Other physicians at Other UCARE personnel in the care of patients with physician the UCARE personnela COVID-19 during the pandemic Not involved, % (n) 61.8 (55) 44.8 (39) 51.8 (43) Yes, in outpatient 17.9 (16) 30.8 (26) 20.4 (17) clinics, % (n) Yes, in inpatient clinics, 25.7 (23) 43.6 (38) 36.1 (30) % (n) Yes, in intensive care 3.3 (3) 9.2 (8) 13.2 (11) unit, % (n) a For example, nurse and technician Changes in consultation patterns during the pandemic Face-to-Face * Phone Calls * Skype Calls * * * Before Pandemic Whatsapp * During Pandemic Messenger *: P < 0.0005 * * * **: P < 0.05 ***: P > 0.05 Zoom * * E-mail * Telemedicine software * 0% 20% 40% 60% 80% 100% F I G U R E 2 The changes in CU consultation patterns during the pandemic Changes made in the ongoing treatments for CU during the pandemic AHs at standard doses AHs at higher doses Omalizumab No change Discontinuation Cyclosporine-A Dose reduction/Interval Extension Systemic CS 0% 20% 40% 60% 80% 100% F I G U R E 3 General approach to ongoing treatments for CU during the pandemic The use of patient-reported outcome measures decreased mark- edly during the COVID-19 pandemic, for the Urticaria Activity Score 3.3 | Cyclosporine and systemic corticosteroids, /Angioedema Activity Score from 65.6% to 47.3%, the Urticaria/ but not antihistamines or omalizumab, are used less Angioedema Control Test from 62.6% to 42.7%, the Dermatology Life during the pandemic Quality Index from 33.0% to 15.1%, the Chronic Urticaria Quality-of-Life Questionnaire from 30.2% to 10.8%, and for the Angioedema Urticaria Regarding ongoing treatments, the general approach of most Quality-of-Life questionnaire from 17.9% to 8.9% (all p < 0.0005). UCAREs during the pandemic was to discontinue or reduce the dose | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 824 KOCATÜRK et al. Preferences in initiation of treatment for CU during the pandemic AHs at standard doses AHs at higher doses Omalizumab Same as before the pandemic Preferred more Preferred less Cyclosporine-A Systemic CS 0% 20% 40% 60% 80% 100% F I G U R E 4 Change in the preferences in initiation of treatment for CU during the pandemic TA B L E 3 Characteristics of the CU Characteristics Mean±SD/%(n) patients diagnosed with COVID-19 Mean number of CU patients diagnosed with COVID−19 per 0.78 ± 1.65 (0–10) (n = 79) center Mean age 43.04 ± 12.08 (18–68) Gender Female 75.9 (60) Comorbidities None 49.4 (38) Hypertension 22.1 (17) Diabetes mellitus 7.8 (6) Asthma 6.5 (5) Hypothyroidism 5.2 (4) Active CU treatment Antihistamines at standard doses 21.5 (17) at the time of the Antihistamines at higher than 22.8 (18) diagnosis standard doses Omalizumab 24 (19) Cyclosporine A 2.5 (2) Omalizumab and antihistamines 10.1 (8) Ligelizumab 1.3 (1) Methotrexate 1.3 (1) Omalizumab, antihistamines, and 1.3 (1) systemic corticosteroids Outcome of Ambulatory 86.1 (68) COVID−19 Hospitalized—mild disease 10.1 (8) Hospitalized—severe disease 3.8 (3) The course of CU No change 55.7 (44) during COVID−19 Better 7.6 (6) Worse 36.7 (29) of systemic corticosteroids (n = 51, 57.3%) and cyclosporine (n = 49, who contract COVID-19, and almost all (92.6%) agreed that omali- 55.7%) and to continue antihistamine (n = 92; 98.9%) and omali- zumab can be continued. In contrast, only 24.2% agreed that immu- zumab treatment (n = 82, 87.2%; Figure 3). nosuppressive treatments can be continued. All of the responding UCARE physicians agreed that antihista- As for the initiation of new treatments during the pandemic, mines at standard or higher doses can be continued in CU patients most UCAREs used cyclosporine (n = 69; 78.4%) and systemic | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License KOCATÜRK et al. 825 TA B L E 4 Number of patients with Severity of COVID−19 a mild course of COVID-19, treated as outpatients or inpatients and number CU treatment at time of Mild disease Mild disease Severe disease of hospitalized patients with severe COVID−19 diagnosis outpatient care hospitalized hospitalized4 COVID-19 and the treatment they AHs only1 29 6 - received for their CU at the time they were diagnosed with COVID-19 Omalizumab2 24 1 2 Immunosuppression3 3 1 - No active treatment 2 - 1 Unspecified 9 - - Ligelizumab 1 - - 1 2 3 At standard or higher doses, ± AHs, includes cyclosporine, systemic corticosteroids, methotrexate ±AHs, and/or omalizumab.4The three patients who were hospitalized were 45, 54, and 65 years old. Two of them were male. The female patient was obese, the others had no comorbidities. In two of them, the CU got worse. TA B L E 5 The link of COVID-19 severity and CU exacerbation CU Course Non-hospitalized Hospitalized Better 7.3 (5) 9.1 (1) No change 61.8 (42) 18.2 (2) Worse 30.9 (21) 72.7 (8) Patients with exacerbation of CU No exacerbation of CU Hospitalized 27.6 (8) 6 (3) Non-hospitalized 72.4 (21) 94 (47) corticosteroids (n = 56; 61.5%) less often, but omalizumab as often 4 | DISCUSSION as before (n = 72; 77.4%; Figure 4). This is the first study on the effects of the COVID-19 pandemic on patients with CU and their care at specialist centers. Our find- 3.4 | Chronic urticaria does not appear to ings show that the pandemic severely impairs CU patient care at affect the course of COVID-19, but COVID-19 results UCAREs, markedly changes physician-patient interactions, and af- in CU exacerbation in one of three patients fects how patients are treated. Our results also indicate that CU is not linked to severe COVID-19, but often worsened by it. Of 79 CU patients with COVID-19 (76% female, mean age: CU is a chronic condition that often comes with fluctuating disease 43.0 ± 12.1 years; 18–68), 76 (96%) showed a mild course of COVID- activity and with severe disease and insufficient treatment response to 19, with 11% and 89% of them receiving inpatient and outpatient antihistamines in most patients. Access to specialized urticaria centers care, respectively. Only 3 patients had severe disease and none died such as UCAREs is therefore crucial, and our data illustrate that this (Table 3). Forty-four (55.7%) of CU patients were on antihistamines, access is severely restricted by the pandemic, with less than half of pa- 26 (32.9%) on omalizumab, and 2 (2.5%) on cyclosporine at the time tients seen at UCAREs than before the pandemic. The short- and long- of their COVID-19 diagnosis. No change in CU treatment was made term consequences of this remain to be seen but must be expected to in 70.9% of the patients following COVID-19 diagnosis (Table 4). include deterioration of disease control, increased impairment of qual- There was no statistically significant relationship between CU treat- ity of life, loss of productivity, and higher rates of frustration, depres- ment and COVID-19 severity (mild vs severe disease). sion, and anxiety in affected patients. Decreased patient referrals are a The course of CU did not change in 55.7% of the patients, while main reason for the decline in patient consultations. This suggests that 36.7% were reported to experience exacerbation and 7% improved. referring physicians, but also patients, should be informed that it is im- Patients who experienced exacerbation of their CU upon contracting portant to continue to seek the help of UCAREs. Referring physicians COVID-19 more often required hospitalization because of the course and patients should be made aware of remote consultation services of their COVID-19, in 28% vs 6% of cases. Vice versa, the rate of CU that UCAREs offer and be encouraged to use them. exacerbation in hospitalized patients was higher than in non-hospital- How does the COVID-19 pandemic affect the way UCAREs inter- ized patients (73% vs 31%; p < 0.05; Table 5). act with their patients? During the pandemic, preventive measures | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 826 KOCATÜRK et al. have been implemented worldwide to adjust outpatient healthcare Given the possible role of mast cells in COVID-19–related lung services and decrease direct patient contacts to a minimum, in line damage and the results of a recent study of the effects of H1 and H2 with current recommendations.10 Our study shows that UCAREs are antihistamines in patients with COVID-19, antihistamine treatment very much on board with this strategy: The rate of face-to-face con- may have added benefit during the pandemic. Although the study was sultations decreased by 62%, from 90% of consultations to less than not randomized, placebo-controlled, or blinded, the combined use of half, whereas the rate of remote consultations, mainly done by phone H1 and H2 antihistamines led to decreased mortality compared to lit- calls and WhatsApp, increased by more than 600%, from one in 10 erature data in patients with severe to critical pulmonary COVID-19 consultations to more than two thirds. Remote consultations have symptoms.29 The same may be true for omalizumab. A meta-analy- 20,21 been shown to be a useful tool during the COVID-19 pandemic, sis of randomized controlled trials in chronic spontaneous urticaria but the long-term consequences of remote care for patients with CU showed similar rates of upper respiratory tract infections in omali- in terms of costs, benefits, impact on physician/patient relation, data zumab and placebo-treated patients.30 Also, omalizumab treatment protection and confidentiality, comfort, risk of malpractice, and ef- was reported to reduce disease duration and viral shedding in rhinovi- fectiveness of disease management remain to be characterized. 22,23 rus infection in children with asthma,31 possibly by enhancing anti-vi- CURICT, a recent UCARE study of the use of Internet and com- ral immunity via downregulation of the high-affinity IgE receptor on munication technologies (ICTs) by patients with urticaria, found that plasmacytoid dendritic cells (pDCs), which are essential for anti-viral almost all CU patients have access to ICTs and that most patients immune responses.32 Moreover, recent reports have demonstrated 24 use ICTs regularly to obtain CU-related information. As for the the effective and safe use of omalizumab in COVID-19 patients with interaction of patients with their physicians, WhatsApp and email urticaria, asthma, and urticarial vasculitis.18 Based on these data, the 25 were the preferred ICTs, similar to patients with asthma or cancer. most recent recommendations by several groups of experts are to WhatsApp is the most popular messaging service around the world continue omalizumab treatment in CU patients with mild-to-moderate and allows smartphone users to exchange texts, images, videos, and COVID-19 course, or when SARS-CoV-2 infection is suspected, and to 26 audio messages. In our study, WhatsApp was the second most pre- only consider prolongation of the injection interval or treatment inter- ferred ICT used for remote consultations by UCAREs, after phone ruption in CU patients with severe COVID-19 course.11 UCAREs share calls. The use of WhatsApp comes at low or no costs, but there are this view, with 93% in agreement that omalizumab can be continued in concerns of patient data protection and confidentiality. Clearly, CU patients with COVID-19. there is a need for the improvement of remote care of patients and In contrast, the majority of UCAREs (78.4% and 61.5%, re- the use of inexpensive, safe, and accessible tools for this. spectively) reported that they use cyclosporine and systemic cor- The reduced use of patient-reported outcome measures ticosteroids less often since the onset of the pandemic regardless (PROMs) during the pandemic is a major cause of concern. PROMs of whether patients have COVID-19 or not. Ongoing treatments guide treatment decisions and help to monitor treatment outcomes. with these agents were discontinued or the dose was modified in Current guidelines recommend the use of PROMs to assess disease more than 50% of patients. This change in CU management is sup- activity, impact, and control at every CU patient visit. PROMs may ported by the increased risk of infection that comes with these ther- be especially helpful during the current pandemic, with disease ac- apies, both showing strong and non-selective immunosuppressive tivity, impact, and loss of control expected to increase in many pa- effects.33,34 Three out of four UCAREs (76%) agree that immuno- tients with CU. The UCARE network is currently developing means suppressive treatments should be discontinued in CU patients with for administering and reviewing CU PROMs remotely, a timely and COVID-19. As of now, there are very few studies on the global im- much needed effort. pact of the pandemic on other specialties and patient populations. Our study shows that the COVID-19 pandemic does not sig- From what has been published, other specialties and the care for nificantly affect the use of first-, second-, and third-line therapies patients with chronic diseases appear to be affected in similar ways for CU at expert centers. Ongoing treatments with antihistamines and extent as compared to what we found to be the case for CU. and omalizumab were maintained and dosing was not modified by This also relates to the changes in treatment linked to the pandemic. most UCAREs (98.9% and 87.2%, respectively). Also, the initiation A recent study performed among allergists, for example, reported of antihistamine and omalizumab treatment has not changed at most that one third of participating physicians stopped systemic steroid UCAREs during the pandemic (96.8% and 77.4%, respectively). This treatment in their patients with asthma.35 Another study performed is in line with current recommendations for urticaria and other mast among rheumatologists found that one third of participating physi- 10,11,27,28 cell-driven diseases. With respect to the implementation of cians reported that at least 10% of their patients had self-discontin- international guidelines during the pandemic, the first three lines ued or reduced their immunosuppressive medication to mitigate the of treatments, that is, a standard-dose antihistamine, an updosed risk of COVID-19.36 antihistamine, and omalizumab, should be continued to be used as Does chronic urticaria affect the course of COVID-19? The re- recommended. The use of immunosuppressive therapies for CU in- sults of our study suggest that this is not the case, but the number cluding the fourth-line treatment cyclosporine should be avoided if of patients analyzed was low. Most COVID-19 patients show a mild possible, emphasizing the need for the development of novel and (40%) or moderate (40%) course, whereas 15% develop severe dis- non-immunosuppressive treatments for CU. ease and need oxygen support, and 5% have critical disease with | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License KOCATÜRK et al. 827 respiratory failure, acute respiratory distress syndrome (ARDS), sep- care and how to overcome it. Finally, we need to better understand sis and septic shock, thromboembolism, and/or multiorgan failure, the interplay between COVID-19 and other viral infections and CU, including acute kidney injury and cardiac injury.37 Of the 79 patients its mechanisms, and strategies to protect CU patients from COVID- with CU and COVID-19 in our study, 96% showed a mild course of 19–induced CU exacerbation. COVID-19, with 11% and 89% receiving inpatient and outpatient Our study shows that CU does not appear to increase the risk for care, respectively. Only 4% of our CU patients had a severe course of a severe course of COVID-19, even in patients on biological treat- COVID-19. The course of COVID-19 in CU patients did not seem to ment. Physicians who take care of patients with CU must be aware be affected by their urticaria treatment. More data are needed, from of the fact that those patients who contract COVID-19 are likely to CU patients with COVID-19 and age- and sex-matched controls. The experience exacerbation of their CU. It is, therefore, important to CU patients in our study were mostly young adults and female, fea- help patients to achieve and maintain control of their disease during tures linked to mild COVID-19. the pandemic. We recommend maintaining ongoing treatments with Does COVID-19 affect the course of CU? COVID-19, in more antihistamines and omalizumab, and to be very cautious with the use than a third of patients (36%), resulted in CU exacerbation, and exac- of immunosuppressives for CU. erbation was more common in patients hospitalized for COVID-19, that is, patients with severe COVID-19. From a clinical perspective, AC K N OW L E D G M E N T S this does not come as a surprise. There are more than 200 reports of We thank Laura Schwenner for her help in distributing the question- acute urticaria associated with COVID-19, which were reviewed in naire and establishing communication between UCAREs. 38 a recent analysis. More than half of these cases of acute urticaria (55%) presented during or preceding COVID-19 infection, disap- C O N FL I C T O F I N T E R E S T peared or improved in most of the cases in less than one week, and Dr. Kocaturk received personal fees from Novartis, Sanofi and responded favorably to treatment with AHs and topical and systemic Menarini. Dr. Salman reports personal fees from Novartis and corticosteroids. Viral infections, including infections with corona vi- İbrahim Etem-Menarini, outside the submitted work. Dr. Cherrez- ruses, are known triggers of CU worsening,39 although more data on Ojeda reports grants from Universidad Espiritu Santo, outside the the rates and relevance of this are needed. From a pathomechanistic submitted work. Dr. Criado reports personal fees from Novartis and perspective, mast cells, the key drivers of CU pathogenesis, can be Takeda, during the conduct of the study; personal fees from Novartis activated by viruses through Toll-like receptors (TLR-4, TLR-7, and and Takeda, outside the submitted work. Dr. Peter has nothing to TLR-9), FcεR1, and complement receptors to release pro-inflamma- disclose. Dr. Cömert Özer has nothing to disclose. Dr. Abuzakouk has tory mediators and cytokines. Both SARS-CoV-1 and SARS-CoV-2 nothing to disclose. Dr. Agondi reports other from Novartis, outside induce the release of IL-6, IL-1, and TNF-α by mast cells, consistent the submitted work. Dr. Al-Ahmad has nothing to disclose. Dr. 15 with the inflammatory profile observed following infection. This Altrichter reports grants and personal fees from Allakos, grants and mechanism may also explain the onset of acute urticaria in COVID- personal fees from AstraZeneca, non-financial support from Moxie, 19 patients. grants from Sanofi, CSL Behring, and Novartis, outside the submit- Stress may be another factor linking COVID-19 to exacerbation ted work. Dr. ARNAOUT has nothing to disclose. Dr. Asero received of CU. The COVID-19 pandemic comes with increased rates of el- honoria (speaker) from Novartis. Dr. Bauer reports grants, personal evated levels of psychological distress in the general population40 fees, and other from Novartis, and personal fees and other from and even higher rates in COVID-19 patients, linked to social isola- Sanofi, during the conduct of the study. Dr. Ben-Shoshan received tion, the psychological impact of a novel severe and potentially fatal honoraria from Novartis. Dr. Bernstein reports grants and personal 41 illness, concerns about infecting others, and stigma. Stress leads fees from Novartis, Genentech, AstraZeneca, Sanofi Regeneron, and to increased levels of neuropeptides such as substance P, which acti- from Allakos, outside the submitted work. He is a UCARE member vates mast cells via the MRGPRX2. Stress is a well-known trigger of site and a member of the JTF practice parameter committee. Dr. CU exacerbations.42-45 Bizjak reports personal fees from Novartis, outside the submitted The strengths of our study include its global approach and scope, work. Dr. BOCCON-GIBOD has nothing to disclose. Dr. Bonnekoh the high response rate of participating UCAREs, and the comprehen- received honoria (advisory board, speaker) from Novartis. Dr. sive assessment of the impact of the pandemic on CU patients and Bouillet reports grants and non-financial support from Novartis, their care at specialist centers. As for limitations, our study of CU grants, personal fees, and non-financial support from Takeda, grants patients with COVID-19 is preliminary, since the number of patients and non-financial support from Behring, and non-financial support included is low and we did not include controls; our study is a global from Pharming and GSK, outside the submitted work. Dr. Brzoza has one, but does not include results from all countries and may, there- nothing to disclose. Dr. Busse reports grants and personal fees from fore, not be representative of the situation and CU patient popula- CSL Behring, Shire/Takada, Pharming, BioCryst, Novartis, and tions in countries without UCAREs. Clearly, many questions remain ResTORbio, personal fees from Pearl Therapeutics, CVS Health, Law to be answered. We need to learn more about the rate of acute ur- offices of Levin, Riback, Adelman, Flangel, AstraZeneca, GSK, ticaria linked to COVID-19 and the rate of progression to chronicity. Vedder Price, and Fresenius, and non-financial support from More information is needed on the limitations of remote CU patient Hereditary Angioedema Association, American Academy of Allergy, | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 828 KOCATÜRK et al. Asthma, and Immunology, outside the submitted work. Dr. Campos nothing to disclose. Dr. Ramon has nothing to disclose. Dr. Rodriguez- has nothing to disclose. Dr. Carne has nothing to disclose. Dr. Conlon Gonzalez has nothing to declare. Dr. Rosario has nothing to declare. reports grants from Novartis and grants from Takeda, outside the Dr. Rudenko has nothing to disclose. Dr. Rutkowski has nothing to submitted work. Dr. Criado reports personal fees from Takeda and disclose. Dr. SANCHEZ has nothing to disclose. Dr. Schliemann re- Novartis, during the conduct of the study; and personal fees from ports grants and personal fees from Novartis Pharma GmbH, out- Takeda and Novartis, outside the submitted work. Dr. Demir has side the submitted work. Dr. Sekerel has nothing to disclose. Dr. nothing to disclose. Dr. Dissemond reports personal fees and other Serpa has nothing to disclose. Dr. Serra-Baldrich has nothing to dis- from Novartis, during the conduct of the study. Dr. Dogan Gunaydin close. Dr. Soria has nothing to disclose. Dr. Staevska has nothing to has nothing to disclose. Dr. Dorofeeva has nothing to disclose. Dr. disclose. Dr. Staubach reports grants, personal fees, non-financial ENSINA reports personal fees from Novartis, and personal fees and support, and other from AbbVie, Allergika, Almirall-Hermal, Amgen, non-financial support from SANOFI, outside the submitted work. Dr. Beiersdorf, Biocryst, Biogen Idec, BMS, Boehringer-Ingelheim, Ertaş has nothing to disclose. Dr. Ferrucci has nothing to disclose. Dr. Celgene, CSL-Behring, Eli-Lilly, Galderma, Hexal, Janssen, FIGUERAS NART has nothing to disclose. Dr. Fomina has nothing to Klosterfrau, LEO-Pharma, LETI-Pharma, L´Oreal, Medice, Novartis, disclose. Dr. Franken has nothing to disclose. Dr. Fukunaga reports Octapharma, Pfizer, Pflüger, Pharming, Regeneron, Shire, Takeda, grants and honoraria as a speaker from Novartis, Taiho, and hono- Regeneron, Sanofi-Genzyme, and UCB Pharma. Dr. Tagka has noth- raria as a speaker from Sanofi, Kyowa Kirin, Tanabe, Korin and ing to disclose. Dr. Takahagi reports personal fees from Novartis Takeda, outside the submitted work. Dr. Giménez-Arnau reports Pharma, outside the submitted work. Dr. Thomsen reports grants grants and personal fees from Uriach Pharma, grants, personal fees and other from Novartis, during the conduct of the study. Dr. and other from Novartis Pharma, personal fees and other from Treudler reports grants and personal fees from Sanofi Genzyme, Sanofi, grants from GSK, grants from Instituto Carlos III FEDER, per- personal fees from ALK-Abello, Takeda, Novartis, and AbbVie, other sonal fees from Menarini, personal fees from Amgen, personal fees from Fraunhofer-IZI Leipzig, and grants from Hautnetz Leipzig/ from Thermo Fisher, and personal fees from Avene, outside the sub- Westsachsen e.V., outside the submitted work. Dr. Vadasz has noth- mitted work. Dr. Godse has nothing to disclose. Dr. Gonçalo reports ing to disclose. Dr. Valle has nothing to disclose. Dr. van Doorn re- personal fees from Novartis Pharma and Sanofi Genzyme, outside ports grants and personal fees from Novartis, and personal fees the submitted work. Dr. Gotua has nothing to disclose. Dr. Grattan from LEO Pharma, AbbVie, BMS, Celgene, Lilly, MSD, Pfizer, Sanofi has nothing to disclose. Dr. Guillet has nothing to disclose. Dr. Genzyme, Janssen Cilag, outside the submitted work. Dr. Vestergaard Inomata has nothing to disclose. Dr. Jakob reports grants, personal reports grants and personal fees from Novartis, and grants and per- fees, and non-financial support from Novartis, during the conduct of sonal fees from Sanofi, outside the submitted work. Dr. Wagner re- the study; grants, personal fees, and non-financial support from ceived a grant from Novartis Pharma GmbH and honoraria for ALK-Abello, personal fees from Bencard/Allergy Therapeutics, lectures or Advisory boards from Novartis Pharma GmbH, ALK- Thermo Fisher, Celgene, and Allergopharma, outside the submitted Abello, Allergopharma, Takeda, and AbbVie. Dr. Wang has nothing to work. Dr. Karakaya has nothing to disclose. Dr. Kasperska-Zając has disclose. Dr. Wedi reports grants, personal fees, non-financial sup- nothing to disclose. Dr. Katelaris has nothing to disclose. Dr. Košnik port, and other from Novartis, grants, personal fees, and non-finan- has nothing to disclose. Dr. Krasowska has nothing to disclose. Dr. cial support from Shire, and personal fees from ALK-Abéllo, Kulthanan has nothing to disclose. Dr. KUMARAN has nothing to HAL-Allergy, Bencard, CSL Behring, and Leo Pharma, outside the disclose. Dr. Lang has nothing to disclose. Dr. Larco reports personal submitted work. Dr. Xepapadaki reports personal fees from Uriach, fees from Novartis, Sanofi, and Faes Farma, outside the submitted Novartis, Nestle, and Nutricia, outside the submitted work. Dr. Yucel work. Dr. Lazaridou has received grants, or honoraria as a speaker or has nothing to disclose. Dr. Zalewska-Janowska has nothing to dis- participant in advisory boards from AbbVie, Novartis, Janssen, Leo close. Dr.Zhao has nothing to disclose. R. Dr. Zuberbier reports per- Pharma, Lilly, Sanofi, Roche, Genesis, UCB, and Pfizer. Dr. Leslie re- sonal fees from Bayer Health Care, FAES, Novartis, Henkel, null, null, ports personal fees from Novartis and Menlo Therapeutics, outside Novartis, Henkel, AstraZeneca Fee for talk, AbbVie Fee for talk, ALK the submitted work. Dr. Lippert reports grants, personal fees, non- Fee for talk, Almirall Fee for talk, Astellas Fee for talk, Bayer Health financial support, and other from Novartis Pharma GmbH, during Care Fee for talk, Bencard Fee for talk, Berlin Chemie Fee for talk, the conduct of the study; personal fees, non-financial support, and FAES Fee for talk, HAL Fee for talk, Leti Fee for talk, Meda Fee for other from Sanofi Genzyme; personal fees and non-financial support talk, Menarini Fee for talk, Merck Fee for talk, MSD Fee for talk, from Takeda Pharma GmbH, outside the submitted work. Dr. Novartis Fee for talk, Pfizer Fee for talk, Sanofi Fee for talk, Calderon has nothing to disclose. Dr. Makris reports personal fees Stallergenes Fee for talk, Takeda Fee for Teva Fee for talk, UCB Fee from Novartis, outside the submitted work. Dr. Marsland reports for talk, Henkel Fee for talk, Kryolan Fee for talk, and L'Oréal Fee for grants and personal fees from Novartis; personal fees from Roche talk outside the submitted work. Dr. Mauer reports grants and per- and Almirall; and personal fees and non-financial support from sonal fees from Allakos, argenx, CSL Behring, FAES, Genentech Sanofi and Galderma, outside the submitted work. Dr. Palitot has Menarini, Moxie, Novartis, Sanofi/Regeneron, UCB, GI innovation, nothing to disclose. Dr. Parisi has nothing to disclose. Dr. Pickert has and Uriach, personal fees from Aralez and Celldex, grants from | 13989995, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/all.14687 by Readcube (Labtiva Inc.), Wiley Online Library on [15/03/2023]. 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