Age-Related Differences in Immunological Responses to SARS-CoV-2
Lydia Su Yin Wong, MRCPCH, Evelyn Xiu Ling Loo, PhD, Alicia Yi Hui Kang, BSc, Hui Xing Lau, BScb, Paul Anantharajah Tambyah, MD, and Elizabeth Huiwen Tham, MRCPCH
There is a striking age-related disparity in the prevalence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 infections, which might be explained by age-dependent immunological mechanisms. These include age-related physiological differences in immunological responses, cross-neutralizing antibodies, and differences in levels and binding affinity of angiotensinconverting enzyme 2, the SARS-CoV-2 target receptor; antibodydependent enhancement in adults manifesting with an overexuberant systemic inflammation in response to infection; and the increased likelihood of comorbidities in adults and the elderly. Emerging immunological phenomena such as Pediatric Multi-System Inflammatory Disorder Temporally associated with SARS-CoV-2 or Multisystem Inflammatory Syndrome in Children are now being observed, though the underlying mechanisms are still unclear. Understanding the mechanisms through which pediatric patients are protected from severe novel coronaviruses infections will provide critical clues to the pathophysiology of coronavirus disease 2019 infection and inform future therapeutic and prophylactic interventions. Asymptomatic carriage in children may have major public health implications, which will have an impact on social and health care policies on screening and isolation practices, school reopening, and safe distancing requirements in the community.
Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement
Alessandra Vultaggio, Ioana Agache, Cezmi A. Akdis, Mubeccel Akdis, Sevim Bavbek, Apostolos Bossios,| Jean Bousquet, Onur Boyman, Adam M. Chaker, Susan Chan, Alexia Chatzipetrou, Wojciech Feleszko, Davide Firinu, Marek Jutel, Paula Kauppi, Ludger Klimek, Antonios Kolios, Akash Kothari, Marek L. Kowalski, Andrea Matucci, Oscar Palomares, Oliver Pfaar, Barbara Rogala, Eva Untersmayr, Thomas Eiwegger
The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a “cytokine storm” and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
Dietary patterns in childhood and their effect on gut microbiota—an Asian perspective on atopy risk
Intan Hakimah Ismail, MMed, PhD, Christophe Lay, PhD, Noorizan H.A. Majid, MM Way Seah Lee, MD, Bee Wah Lee, MD, Amir Hamzah Abdul Latiff, MMed, MRCP, Hern Tze Tina Tan, PhD, Jan Knol, PhD, and Yeong Yeh Lee, MD, PhD
EAACI Guidelines on the effective transition of adolescents and young adults with allergy and asthma
Graham Roberts, Marta Vazquez-Ortiz, Rebecca Knibb, Ekaterina Khaleva, Cherry Alviani, Elizabeth Angier, Katharina Blumchen, Pasquale Comberiati, Bettina Duca, Audrey DunnGalvin, Teresa Garriga-Baraut, Claudia Gore, M. Hazel Gowland, Valérie Hox, Britt Jensen, Charlotte G. Mortz, Oliver Pfaar, Helena Pite, Alexandra F. Santos, Silvia Sanchez-Garcia,Frans Timmermans
Adolescent and young adult (AYA) patients need additional support, while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process, which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multidisciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include the following: (a) starting transition early (11-13 years), (b) using a structured, multidisciplinary approach, (c) ensuring AYA fully understand their condition and have resources they can access, (d) active monitoring of adherence and (e) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (a) simplifying medication regimes and using reminders; (b) focusing on areas where AYA are not confident and involving peers in training AYA patients; (c) identifying and managing psychological and socio-economic issues impacting disease control and quality of life; (d) enrolling the family in assisting AYA to undertake self-management; and (e) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.
Fasting, dietary restriction, and immunosenescence
Valter D. Longo, PhD, and Salvatore Cortellino, PhD
Highways to hell: Mechanism-based management of cytokine storm syndromes
Scott W. Canna, MD, and Randy Q. Cron, MD, PhD
Since the first textbook devoted to cytokine storm syndromes (CSSs) was published in 2019, the world has changed dramatically and the term’s visibility has broadened. Herein, we define CSSs broadly to include life/organ-threatening systemic inflammation and immunopathology regardless of the context in which it occurs, recognizing that the indistinct borders of such a definition limit its utility. Nevertheless, we are focused on the pathomechanisms leading to CSSs, including impairment of granule-mediated cytotoxicity, specific viral infections, excess IL-18, and chimeric antigen receptor T-cell therapy. These mechanisms are often reflected in distinct clinical features, functional tests, and/or biomarker assessments. Moreover, these mechanisms often indicate specific, definitive treatments. This mechanism-focused organization is vital to both advancing the field and understanding the complexities in individual patients. However, increasing evidence suggests that these mechanisms interact and overlap. Likewise, the utility of a broad term such as ‘‘cytokine storm’’ is that it reflects a convergence on a systemic inflammatory phenotype that, regardless of cause or context, may be amenable to ‘‘inflammo-stabilization.’’ CSS research must improve our appreciation of its various mechanisms and their interactions and treatments, but it must also identify the signs and interventions that may broadly prevent CSS-induced immunopathology.
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 Gutermuth1 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.
Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy
Ann-Marie Malby Schoos, Dominique Bullens, Bo Lund Chawes, Joana Costa, Liselot De Vlieger, Audrey DunnGalvin, Michelle M. Epstein, Johan Garssen, Christiane Hilger, Karen Knipping, Annette Kuehn, Dragan Mijakoski, Daniel Munblit, Nikita A. Nekliudov, Cevdet Ozdemir, Karine Patient, Diego Peroni, Sasho Stoleski, Eva Stylianou, Mirjana Tukalj, Kitty Verhoeckx, Mihaela Zidarn and Willem van de Veen on behalf of Core Outcome Measures for Food Allergy (COMFA) consortium
IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.
Pediatric Asthma Health Care Utilization, Viral Testing, and Air Pollution Changes During the COVID-19 Pandemic
Kiara Taquechel, BS, Avantika R. Diwadkar, MS, Samir Sayed, BS, Jesse W. Dudley, MS, Robert W. Grundmeier, MD, Chén C. Kenyon, MD, MS, Sarah E. Henrickson, MD, PhD, Blanca E. Himes, PhD, and David A. Hill, MD, PhD
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused dramatic changes in daily routines and health care utilization and delivery patterns in the United States. Understanding the influence of these changes and associated public health interventions on asthma care is important to determine effects on patient outcomes and identify measures that will ensure optimal future health care delivery. OBJECTIVE: We sought to identify changes in pediatric asthma-related health care utilization, respiratory viral testing, and air pollution during the COVID-19 pandemic.
METHODS: For the time period January 17 to May 17, 2015 to 2020, asthma-related encounters and weekly summaries of respiratory viral testing data were extracted from Children’s Hospital of Philadelphia electronic health records, and pollution data for 4 criteria air pollutants were extracted from AirNow. Changes in encounter characteristics, viral testing patterns, and air pollution before and after Mar 17, 2020, the date public health interventions to limit viral transmission were enacted in Philadelphia, were assessed and compared with data from 2015 to 2019 as a historical reference.
RESULTS: After March 17, 2020, in-person asthma encounters decreased by 87% (outpatient) and 84% (emergency D inpatient). Video telemedicine, which was not previously available, became the most highly used asthma encounter modality (61% of all visits), and telephone encounters increased by 19%. Concurrently, asthma-related systemic steroid prescriptions and frequency of rhinovirus test positivity decreased, although air pollution levels did not substantially change, compared with historical trends.
CONCLUSIONS: The COVID-19 pandemic in Philadelphia was accompanied by changes in pediatric asthma health care delivery patterns, including reduced admissions and systemic steroid prescriptions. Reduced rhinovirus infections may have contributed to these patterns.
Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation
Haiyu Hong, Shumin Liao, Fenghong Chen, Qintai Yang, De-Yun Wang
Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium-derived cytokines, namely IL-25, IL-33, and TSLP, as key regulatory factors that link in immune-pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium-derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.