key: cord-271930-9a18h2tr
authors: Licari, Amelia; Votto, Martina; Brambilla, Ilaria; Castagnoli, Riccardo; Piccotti, Emanuela; Olcese, Roberta; Tosca, Maria Angela; Ciprandi, Giorgio; Marseglia, Gian Luigi
title: Allergy and asthma in children and adolescents during the COVID outbreak: What we know and how we could prevent allergy and asthma flares
date: 2020-05-28
journal: Allergy
DOI: 10.1111/all.14369
sha: 
doc_id: 271930
cord_uid: 9a18h2tr

Coronavirus disease 2019 (COVID-19) pandemic is affecting people at any age with a more severe course in patients with chronic diseases or comorbidities, males and elderly patients. The Center for Disease Control and Prevention (CDC) initially proposed that patients with chronic lung diseases, including moderate-severe asthma, and allergy may have a higher risk of developing severe COVID-19 than otherwise healthy people (https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/asthma.html).

positive swab (RT-PCR analysis). The most common symptoms were fever (67.5%), cough (55%), nasopharyngeal complaints (27.5%), and gastrointestinal symptoms (17.5%). No child reported dyspnea, and 8 (20%) children were asymptomatic, anosmia/dysgeusia was present in only 3 (12.5%) subjects, and pneumonia was diagnosed in 4 (10%) children. Twenty-four (60%) children were hospitalized, but only one required oxygen therapy and ICU admission. These outcomes confirmed that COVID-19 in children is usually rare, mild-moderate, and without sex difference, but may affect any age. At present, pediatric COVID-19 concerns about 1% of the entire COVID-19 population.

Several hypotheses have been prospected to explain the clinical feature observed in childhood, including the different frequency of ACE2 expression on pneumocytes, which is higher in the elderly and adult men. ACE2 is the receptor for coronavirus. Thus, overexpression may promote infection. Hypertension, chronic respiratory diseases, cancer, and metabolic disorders were also reported frequent comorbidity, common in older subjects. However, no certain risk factors have been defined still now.

On the other hand, children seem to be protected thanks to some probable mechanisms. Children usually have fewer comorbidity, ACE2 is underexpressed, and they do not smoke (smoking is associated with increased expression of ACE2), have a large thymic repertoire and sustained innate immunity and more T-and B-regulatory lymphocytes than adults, and received an extensive vaccination program. As a result, children could have a more protective immune response than adults.

On the other hand, allergy has been rare comorbidity in Chinese COVID-19 patients. 3, 4 Very recently, it has been reported that eosinopenia was very frequent (81.2%) in patients deceased for COVID-19, 5 so eosinopenia was considered as a biomarker of poor prognosis.

Very recently, eosinopenia was considered the best predictor to facilitate triage of COVID-19 patients. 6 It has been speculated that the reduced eosinophil count was not related to corticosteroid use but related to CD8 T-cell depletion and eosinophil consumption caused by SARS-CoV-2. As ECP and EDN, eosinophil-derived enzymes, can neutralize the virus, the eosinopenia could explain a higher SARS-CoV-2 load that, in turn, overconsumes eosinophils. Eosinophils orchestrate the immune response to a respiratory virus, releasing cytotoxic proteins, increasing NO, producing type 1-associated cytokines, mainly IL-12 and IFN-γ, and recruiting CD8 T lymphocytes. 7 Eosinophils clear viral load, thus guarantying recovery from viral infections. As a consequence, it may be hypothesized that allergic patients, having eosinophilia, are less affected by COVID-19.

The literature data could support this theory. [5] [6] [7] Consistently, we found only two allergic children (food allergy and allergic rhinitis) and one child with asthma. We considered peripheral eosinophils (as absolute and relative) and found low counts (Table 1) . We compared these COVID-19 children with a large group (120) of allergic children. Allergic children had a significantly higher (P < .0001) eosinophil count than COVID-19 patients. Even five (12.5%) COVID-19 children have no (0) eosinophil. Notably, one required admission at the intensive care unit.

To further support the hypothesis that allergy might be "protective," a very recent study provided evidence that allergic sensitization was inversely related to ACE2 expression, and allergen natural exposure and challenge significantly reduced ACE2 expression. 8 These preliminary data need a confirmation that should be provided by more substantial clinical records. However, it has been recently commented that chronic respiratory diseases, including COPD and asthma, seem to be underrepresented in the comorbidities of COVID-19 patients. 9 Therapies could play a possible "protective" effect for respiratory disorders, such as corticosteroids that could contrast viral replication, even though this hypothesis needs confirmation.

The current study has some limitations. The data were derived from the official dataset, but these numbers very probably underestimate the real number of infected people, including asymptomatic subjects. Preliminary unofficial data report a 10% prevalence of positive subjects in the general population, whereas the current prevalence of diagnosed COVID-19 is less than 1%. Moreover, the real prevalence of allergic and asthmatic patients with COVID-19 could be higher if a larger sample were evaluated. Also, the allergic disease prevalence depends on age: The present data concerned young children (median age 5 years). There was also the likelihood that some data on allergy would be missed. Therefore, further study should be performed to confirm this preliminary experience.

On the other hand, children and adolescents with allergy and asthma should be adequately managed during this COVID-19 pandemic, also considering the restrictive rules released by governmental authorities that impose a strict limitation on movements.

Therefore, it is essential to implement a series of strategies to manage allergic and asthmatic children and adolescents. As Moreover, an optimal asthma control should be pursued as a protracted homestay is associated with increased exposure to perennial allergens, including house dust mites, pets, and molds, and indoor pollutants that amplify type 2 inflammation. Also, lack of beneficial physical activity, inactivity, overconsumption of snacks, and cigarette smoking may promote asthma worsening. The counseling represents another critical issue as asthmatic children and adolescents and their parents frequently have emotional disorders that significantly affect asthma and inevitably worsen during this outbreak.

During this viral outbreak, the use of nebulizer may be discouraged unless essential, because the nebulized therapy may allow to aerosolize SARS-CoV-2 and increase the risk of infection, as recently recommended. 10 In summary, the rapid spread of SARS-CoV-2 infection and the lack of specific antiviral therapies and vaccines currently require additional medical efforts to prevent COVID-19 and mostly protect patients with chronic diseases. In conclusion, an efficient social distancing of families with asthmatic children remains the best option to prevent COVID-19. Moreover, the use of masks could also be useful to reduce exposure to pollens.

None.

Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China

SARS-CoV-2 infection in children

Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan

Eleven faces of coronavirus disease 2019

Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational study

Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study

Eosinophil responses during COVID-19 infections and coronavirus vaccination

Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor, ACE2

Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?

COVID-19: pandemic contingency planning for the allergy and immunology clinic