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October 2020

A compendium answering 150 questions on COVID-19 and SARS-CoV-2

Carmen Riggioni; Pasquale Comberiati; Mattia Giovannini; Ioana Agache; Mübeccel Akdis; Magna Alves-Correia; Josep M. Antó; Alessandra Arcolaci; Ahmet Kursat Azkur; Dilek Azkur; Burcin Beken; Cristina Boccabella; Jean Bousquet; Heimo Breiteneder; Daniela Carvalho; Leticia De las Vecillas; Zuzana Diamant; Ibon Eguiluz-Gracia; Thomas Eiwegger; Stefanie Eyerich; Wytske Fokkens; Ya-dong Gao; Farah Hannachi; Sebastian L. Johnston; Marek Jutel; Aspasia Karavelia; Ludger Klimek; Beatriz Moya; Kari C. Nadeau; Robyn O'Hehir; Liam O'Mahony; Oliver Pfaar; Marek Sanak; Jürgen Schwarze; Milena Sokolowska; María J. Torres; Willem van de Veen; Menno C. van Zelm; De Yun Wang; Luo Zhang; Rodrigo Jiménez-Saiz; Cezmi A. Akdis


In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19–related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

Emerging treatments in COVID-19: Adverse drug reactions including drug hypersensitivities

Zita-Rose Manjaly Thomas, Anne Leuppi-Taegtmeyer, Dagmar Jamiolkowski, Esther Steveling-Klein, Felicitas Bellutti-Enders, Kathrin Scherer Hofmeier, and Karin Hartmann, MD

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

Anu Laulajainen‑Hongisto, Annina Lyly, Tanzeela Hanif, Kishor Dhaygude, Matti Kankainen, Risto Renkonen, Kati Donner, Pirkko Mattila, Tuomas Jartti, Jean Bousquet, Paula Kauppi and Sanna Toppila‑Salmi


Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10–8) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR–associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.

Hypersensitivities following allergen antigen recognition by unconventional T cells

Marcela de Lima Moreira, Michael N. T. Souter, Zhenjun Chen, Liyen Loh, James McCluskey, Daniel G. Pellicci, Sidonia B. G. Eckle


Conventional T cells recognise protein-derived antigens in the context of major histocompatibility complex (MHC) class Ia and class II molecules and provide anti-microbial and anti-tumour immunity. Conventional T cells have also been implicated in type IV (also termed delayed-type or T cell–mediated) hypersensitivity reactions in response to protein-derived allergen antigens. In addition to conventional T cells, subsets of unconventional T cells exist, which recognise non-protein antigens in the context of monomorphic MHC class I-like molecules. These include T cells that are restricted to the cluster of differentiation 1 (CD1) family members, known as CD1- restricted T cells, and mucosal-associated invariant T cells (MAIT cells) that are restricted to the MHC-related protein 1 (MR1). Compared with conventional T cells, much less is known about the immune functions of unconventional T cells and their role in hypersensitivities. Here, we review allergen antigen presentation by MHC-Ilike molecules, their recognition by unconventional T cells, and the potential role of unconventional T cells in hypersensitivities. We also speculate on possible scenarios of allergen antigen presentation by MHC-I-like molecules to unconventional T cells, the hallmarks of such responses, and the expected frequencies of hypersensitivities within the human population.

IgE autoantibodies and autoreactive T cells and their role in children and adults with atopic dermatitis

Fariza Mishaal Saiema Badloe, Shauni De Vriese, Katarina Coolens, Carsten B. Schmidt‑Weber, Johannes Ring, Jan Gutermuth and Inge Kortekaas Krohn


The pathophysiology of atopic dermatitis (AD) is highly complex and understanding of disease endotypes may improve disease management. Immunoglobulins E (IgE) against human skin epitopes (IgE autoantibodies) are thought to play a role in disease progression and prolongation. These antibodies have been described in patients with severe and chronic AD, suggesting a progression from allergic inflammation to severe autoimmune processes against the skin. This review provides a summary of the current knowledge and gaps on IgE autoreactivity and selfreactive T cells in children and adults with AD based on a systematic search. Currently, the clinical relevance and the pathomechanism of IgE autoantibodies in AD needs to be further investigated. Additionally, it is unknown whether the presence of IgE autoantibodies in patients with AD is an epiphenomenon or a disease endotype. However, increased knowledge on the clinical relevance and the pathophysiologic role of IgE autoantibodies and self-reactive T cells in AD can have consequences for diagnosis and treatment. Responses to the current available treatments can be used for better understanding of the pathways and may shed new lights on the treatment options for patients with AD and autoreactivity against skin epitopes. To conclude, IgE autoantibodies and self-reactive T cells can contribute to the pathophysiology of AD based on the body of evidence in literature. However, many questions remain open. Future studies on autoreactivity in AD should especially focus on the clinical relevance, the contribution to the disease progression and chronicity on cellular level, the onset and therapeutic strategies.

Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

Milena Sokolowska, Zuzanna M. Lukasik, Ioana Agache, Cezmi A. Akdis, Deniz Akdis, Mübeccel Akdis, Weronika Barcik, Helen A. Brough, Thomas Eiwegger, Andrzej Eljaszewicz, Stefanie Eyerich, Wojciech Feleszko, Cristina Gomez-Casado, Karin Hoffmann-Sommergruber, Jozef Janda, Rodrigo Jiménez-Saiz, Marek Jutel, Edward F. Knol, Inge Kortekaas Krohn, Akash Kothari, Joanna Makowska, Marcin Moniuszko, Hideaki Morita, Liam O'Mahony, Kari Nadeau, Cevdet Ozdemir, Isabella Pali-Schöll, Oscar Palomares, Francesco Papaleo, Mary Prunicki, Carsten B. Schmidt-Weber, Anna Sediva, Jürgen Schwarze, Mohamed H. Shamji, Gerdien A. Tramper-Stranders, Willem van de Veen, Eva Untersmayr


With the worldwide spread of the novel severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease- 19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.

Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement

Jean Bousquet, Cezmi A. Akdis, Marek Jutel, Claus Bachert, Ludger Klimek, Ioana Agache, Ignacio J. Ansotegui, Anna Bedbrook, Sinthia Bosnic-Anticevich, G. Walter Canonica, Tomas Chivato, Alvaro A. Cruz, Wienczyslawa Czarlewski, Stefano Del Giacco, Hui Du, Joao A. Fonseca, Yadong Gao, Tari Haahtela, Karin Hoffmann-Sommergruber, Juan-Carlos Ivancevich, Nikolaï Khaltaev, Edward F. Knol, Piotr Kuna, Desiree Larenas-Linnemann, Joaquim Mullol, Robert Naclerio, Ken Ohta, Yoshitaka Okamoto, Liam O’Mahony, Gabrielle L. Onorato, Nikos G. Papadopoulos, Oliver Pfaar, Boleslaw Samolinski, Jürgen Schwarze, Sanna Toppila-Salmi, Maria-Teresa Ventura, Arunas Valiulis, Arzu Yorgancioglu, Torsten Zuberbier, Ruby Pawankar, the ARIA-MASK Study Group

Past, present, and future of anti-IgE biologics

Pascal Guntern, Alexander Eggel


About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances, scientists have started inventing strategies to block its pathophysiological activity in 1986. The initial concept of specific IgE targeting through the use of anti-IgE antibodies has gained a lot of momentum and within a few years independent research groups have reported successful generation of first murine monoclonal anti-IgE antibodies. Subsequent generation of optimized chimeric and humanized versions of these antibodies has paved the way for the development of therapeutic anti-IgE biologicals as we know them today. With omalizumab, there is currently still only one therapeutic anti-IgE antibody approved for the treatment of allergic conditions. Since its application is limited to the treatment of moderate-to-severe persistent asthma and chronic spontaneous urticaria, major efforts have been undertaken to develop alternative anti-IgE biologicals that could potentially be used in a broader spectrum of allergic diseases. Several new drug candidates have been generated and are currently assessed in pre-clinical studies or clinical trials. In this review, we highlight the molecular properties of past and present anti-IgE biologicals and suggest concepts that might improve treatment efficacy of future drug candidates.

Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: Specific Drugs

Ana Dioun Broyles, MD, Aleena Banerji, MD, and Mariana Castells, MD, PhD

Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: General Concepts

Ana Dioun Broyles, MD, Aleena Banerji, MD, and Mariana Castells, MD, PhD

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