Introduction |Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose correctly these patients. Aim |To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods| Nineteen centers, scattered throughout Italy, participated in the study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked foods, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results| Two hundred and forty-seven individuals with a history of adverse reaction to crustaceans participated in the study. Only 47.8% of them reacted after cephalopod or bivalve ingestion. None of the tests used, either in vivo or in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed with an agreement between in vivo and in vitro tests ranging between 52% and 62% of cases. Skin tests were able to identify the cephalopod and bivalve reactors (p <0.001), also using fresh cooked or raw food (p <0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to the tolerant subjects, but 33% of patients allergic to shellfish were not detected by any of the available molecules. A higher frequency of shrimp hypersensitivity was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south. Conclusion |The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity must still rely on skin tests with fresh material. There is no need to exclude mollusks from shrimp allergic patients’ diet unless clinical history, the available diagnostic instruments, and/or tolerance tests support such a decision. Primary sensitization to mollusks seems possible.

Background: Allergic rhinitis (AR) is a major non-communicable disease that affects the health-related quality of life (HRQoL) of patients. AR is significantly related to asthma also affecting HRQoL. However, data on HRQoL and symptom control in AR patients with comorbid asthma are lacking. Objective: To assess the differences of symptom control and HRQoL in AR patients with and without comorbid asthma. Methods: In this multicentre, cross-sectional study, patients with AR were screened and administered questionnaires of demographic characteristics and health conditions (symptoms/diagnosis of AR and asthma, disease severity level, and allergic conditions). HRQoL was assessed using a modified version of the RHINASTHMA questionnaire and symptom control was evaluated by a modified version of the Control of Allergic Rhinitis/Asthma Test (CARAT). Results: Out of 643 patients with AR, 500 (78%) had asthma as a comorbidity, and 54% had moderate-severe intermittent AR, followed by moderate-severe persistent AR (34%). Patients with both AR and asthma had significantly higher RHINASTHMA scores than the patients with AR alone (e.g., median RHINASTHMA-total score 84 vs. 48.5, respectively). Conversely, CARAT scores were significantly lower in AR with comorbid asthma than in the patients with AR alone (median CARAT-total score 16.5 vs. 23, respectively). Upon stratifying asthma based on severity, AR patients with severe persistent asthma had worse HRQoL and control than AR patients with mild persistent asthma. Conclusions: Our observation of poorer HRQoL and symptoms control in AR patients with comorbid asthma supports the importance of a comprehensive approach for the management of AR in case of a comorbid allergic condition.

Reply to Morais-Almeida.To the Editor,We appreciate Dr. Morais-Almeida’s comments 1 about our Letter to the Editor, presenting additional literature about asthma prevalence in severe COVID-19 patients and highlighting data that contrasts our hypothesis that asthma, particularly type 2 asthma, may be protective against severe disease.The data that protection may be dependent on type 2 immunity is derived from the higher percentage of asthmatics being atopic2, also reflected in the series of ~2,500 patients regularly followed up in our Allergy Unit. Yu et al. 3 provided preliminary evidence about this in a single-center retrospective study, where COVID-19 atopic patients had less severe infections, milder lung damage compared to age- and gender- matched COVID-19 controls.ACE-2, the SARS-CoV-2 receptor, is linked to type 1 and 2 interferon signatures, and found to be overexpressed in type 2-low asthmatics4. Nevertheless, different outcomes in distinct asthma phenotypes still need to be addressed in COVID-19 studies.Besides Italy and China, reports from Russia 5 on ~1,300 intensive care unit patients with SARS-CoV-2 infection confirm the observation of a low prevalence of chronic lung diseases (i.e. asthma as well as COPD).Although preliminary data on the first COVID-19 cases in the US6 seem to contrast these observations, the higher prevalence of asthma in US COVID-19 hospitalised patients should be considered alongside a higher overall prevalence in these countries compared to Europe and China, as well as on the influence of other comorbidities (i.e. obesity) and host factors (i.e. age, race: 33% were non-Hispanic black patients in the study by Garg et al.) impacting COVID-19 outcomes. Another report from Sweden 7highlights the association between severe asthma and severe COVID-19.The severe asthma phenotype is often characterized by mixed granulocytic populations (neutrophilic and eosinophilic), prevalent type 1 inflammation, increased IFN-γ levels in the airways and ineffectiveness of ICS. This severe phenotype by itself, although accounting for less than 5% of asthmatic patients, would justify the CDC (and other institutions) including asthma as a risk factor for COVID-19. Data from the UK 8, apart from confirming the role of additional comorbidities, draw attention to the recent use of oral steroids, which, indeed, may be a clue for uncontrolled and/or severe asthma.Uncontrolled asthma is a risk factor for viral exacerbations and hospitalizations and we embrace the opportunity to stress the importance of optimal adherence to asthma controlling medications, regular follow-up and specialist-assessment of disease activity. Moreover, treatable comorbidities, which may impair asthma control, should always be managed. Promoting vaccination for preventable respiratory infections (i.e. Influenza and Pneumococcal pneumonia) is also advisable. Future studies may help better distinguishing the impact of different asthma phenotypes and comorbidities on COVID-19 outcome.Carli G.1, Cecchi L.1, Stebbing J.2, Parronchi P.3, Farsi A.11 SOS Allergy and Clinical Immunology, USL Toscana Centro, Prato Italy2 Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK3 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy