Article type: Letter to the Editor

Allergy: Letter to the Editor

Background: The aim of this study is to investigate the impact of COVID-19 related treatment delay on subcutaneous immunotherapy (SCIT) efficacy in patients with allergic rhinitis (AR). Methods: The study was performed in 643 patients with SCIT appointments between February 1 and May 31, 2020. The clinical assessment, performed at baseline (V0) and one year later (V1), included visual analogue scale (VAS); daily symptom score (dSS); daily medication score (dMS); combined symptom and medication scores (CSMS); quality of life (QoL); self-rating anxiety scale (SAS); and self-rating depression scale (SDS) for each patient. Results: At V0, 249 patients were treated on schedule, and 394 were delayed (7 ± 4.68 weeks). Among them, 319 patients (105 on schedule, and 214 delayed) also completed the assessments at V1, with the absence of 25.39% patients due to completion of SCIT, and 25.35% patients were withdrawal. The results of all assessments were within the normal range for all patients at V0 and V1, with the exception of a slightly higher SDS score (56.13) at V0. In the SCIT delayed group. there was a significant positive correlation between the length (weeks) of the delay and SDS score, and this was significantly higher in patients with poor control of nasal symptoms. Conclusions: This study showed the long-term efficacy of SCIT for AR patients, including those who have had to delay normal therapy due to the COVID-19 outbreak. The psychological status of SCIT patients in response to lockdown of hospital services during this critical period should be considered.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared to the standard of care. Pubmed, EMBASE and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, reslizumab-1) included 1236 adults, with follow-up 20-64 weeks. Dupilumab reduces the need for surgery (NFS) and oral corticosteroid (OCS) use (RR 0.28; 95%CI 0.20-0.39, moderate certainty) and improves with high certainty smell (mean difference (MD) +10.54; 95%CI +9.24 to +11.84) and quality of life (QoL) (MD -19.14; 95%CI 95%CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95%CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95%CI 0.78 to 0.92, high certainty), decreases OCS use (RR 0.38; 95%CI 0.10-1.38, moderate certainty), improves with high certainty smell (MD +3.84; 95%CI +3.64 to +4.04) and QoL (MD -15.65; 95%CI -16.16 to -15.13), with increased TAE (RR 1.73; 95%CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95%CI 0.64 to 0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95%CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95%CI 0.41-6.50). The evidence for reslizumab is very uncertain.

Modern healthcare requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of the distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions on the efficacy of the current management of allergic diseases requires further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen-immunotherapy with a special emphasis on specific IgE, microbiome and epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

Background: Tight junctions (TJs) are intracellular structures which are essential for epithelial barrier function and play an important role in antimicrobial defense. Epithelium dysfunction and type-2-skewed inflammation are two main pathological phenomena of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of pro-inflammatory type-2 cytokine interleukin-13 (IL-13) on TJs in CRSwNP is poorly understood. Methods: Nasal biopsies of 70 CRSwNP patients and 25 healthy subjects, and in vitro IL-13-matured human nasal epithelial cells (hNECs) in 9 persons were used to analyze epithelial markers and TJ proteins. Epithelium permeability, transepithelial electrical resistance (TEER), mRNA and protein expression of TJs were quantified for IL-13-matured hNECs and that with RV infection. Results: Both mRNA and protein expression of occludin, claudin-3 and ZO-1 were significantly decreased in CRSwNP biopsies and in hNECs after IL-13 treatment. Differentiation of hNECs with IL-13 treatment increased epithelium permeability, decreased TEER and altered hNECs composition resulting in lesser ciliated cells and mucus over-secretion. Interestingly, claudin-3 is selectively expressed on ciliated cells. While RV infection induced minimal changes to TJs, the IL-13-matured hNECs has reduced capacity for upregulation of IFN-λ1 and CXCL10 but further increased the expression of TSLP upon acute RV infection. Conclusions: These findings suggested that IL-13-mediated dysfunction of TJs and compromised epithelial barrier. IL-13-induced cilia loss conferred lowered viral replication and impaired antiviral responses of nasal epithelium against acute RV infection.

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 ~5.6 million confirmed cases and caused 353,334 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socio-economic 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, thrombo-embolic complications and multiorgan failure. The epidemiologic features of 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. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.