Allergy does not appear to be a predisposing factor for the development of SARS CoV-2 infection or an aggravating one in case of disease16.
Dong et al., analyzing children and adults affected by COVID-19, reported that no patients with allergies presented critical symptoms or had a more severe course of illness than those without allergies. All this is in line with the hypothesis of a positive role exerted by the Th2 immune response in COVID-19 pathogenesis 17.
Kimura et al., highlighted that IL-4 and IL-13, typical cytokines of a Th2 response, down-regulating ACE2 receptors in upper airways cells of allergic children, would exert protection against SARS CoV2 infection; otherwise the Th1 response, with interferon-gamma (IFN-gamma) release, increases ACE2 expression, promoting SARS CoV-2 entry into airway cells. All these observations, confirm the role played by the Th1/Th2 balance in the pathogenesis of COVID-19 18.
The systematic review of the literature, conducted by Morais-Almeida et al., supports these results, analyzing the relationship between asthma and COVID-19 in several studies and highlighting no evidence of a higher risk of being infected by SARS CoV2 or to develop a critical illness among asthmatic patients 19.
Hence, according to our results, children with asthma and allergic rhinoconjutivitis present a low prevalence of SARS CoV2 infection, because the ACE2 receptors used by the virus to enter the respiratory tract are less expressed in allergic phenotypes. Conversely, other conventional coronaviruses or respiratory viruses are able to exacerbate asthma because they use other entry receptors different to ACE220.
Moreover, these ACE2 are also down-regulated by asthma therapies that must be continued during the outbreak, according to the international guidelines, to obtain the control of allergic symptoms, also achieved respecting the current social distances and public hygiene recommendations 14.
A good COVID-19 prognosis is also linked to a high blood eosinophil count, common finding in allergic diseases in the context of a Th2 response19. Du Y et al., reported that eosinopenia was found in about 80% of patients died for COVID-19, considering it as a biomarker of worse prognosis and a predictor for the development of COVID-19 severity 21.
So, although asthma and allergic symptoms are often associated to COVID-19 they did not represent risk factors for a more severe disease course and did not lead to a higher frequency of hospitalization 22. These results were also confirmed in a wide online survey conducted on 133.000 asthmatic children who reported mild symptoms and only one case of hospitalization for COVID-19 23.
Moreover, during the pandemic, the lower prevalence of asthmatic and allergic exacerbations is also attributable to greater public health hygiene measures, the use of facemasks, the lockdown periods and a prompter management of respiratory symptoms by parents 24.
Obviously, symptoms of uncontrolled asthma and allergic symptoms, are considered risk factors for the development of severe COVID-19 14 .
For this reason, the Global Initiative for Asthma (GINA) claimed the necessity to achieve asthma control by continuing, even during the pandemic, therapies including biologic drugs, except in patients with active COVID-19 25,26,27.
However, in addition to the management of asthma, also AR requires to be adequately treated 7 because it may have an overlap of symptoms with COVID-19 infectious rhinitis. Uncontrolled AR can increase the risk of viral transmission in children with COVID-19. ARIA and EAACI reiterated the importance of performing a correct nasal therapy with intranasal corticosteroid to avoid the worsening of allergic symptoms and, in case of SARS CoV2 infection, the viral spread 28.
On the other hand, it is recommended to discontinue allergen immunotherapy (AIT), as it decreases the TH2 response, in COVID-19 patients and to continue it in allergic patients without the infection 29,30.
Summarizing, allergic patients present a Th2 response with a lower production of IFN-α in addition to the presence of eosinophils and low ACE2 expression in the airway tact; in addition, asthmatic patients benefit from the antiviral/ immunomodulatory effect exerts by asthma medications 12.
All these factors act as a protective mechanism, reducing the hyperinflammation triggered by the virus to which the more severe clinic is linked.
In line with the literature, the results of both surveys, provide data on the prevalence of allergic rhinoconjuntivitis and asthma symptoms in children affected by COVID-19 nationwide, supporting the concept that controlled allergic symptoms do not constitute risk factors for SARS CoV2 susceptibility.
These results, obtained by the preliminary analysis of the first COVID-19 survey 13, were also confirmed by the second one. In particular, the first survey showed that, in relation to both asthma and allergic rhinoconjunctivitis, the general prevalence was mostly between 0–20% throughout the country. All in all, northern regions showed a lower prevalence of allergic symptoms than the Center and South.
The second survey highlighted a lower prevalence of asthma nationwide in comparison to the first one; in particular it confirmed that the North had the lowest prevalence of both asthma and allergic rhinoconjunctivitis and it reported a marked improvement in the prevalence of both diseases in the Center and South.
Comparing the two surveys, statistically significant differences were reported only in the distribution of asthma prevalence in Southern Italy, while no differences were found in the North and in the Center. Lastly regarding allergic rhinoconjunctivitis distribution, no differences were noticed at a national level.
In support of our findings, another Italian survey conducted among children with AR and/or asthma to evaluate allergic symptoms and the need of drug usage during lockdown, showed an overall trend of clinical improvement and a reduction of on demand and basal therapy for both AR and asthma. All these results can be attributable to various factors: the prompt management of allergic symptoms by parents and the minor exposure to pollens, viruses, and air pollution due to the lockdown 24.
Similar results achieved by the already mentioned survey conducted by Papadopoulos et al., confirmed that children with asthma were not affected to a great extent by COVID-19, due to better adherence to preventive hygiene measures and improved treatment compliance 23.
This study presents also some limitations. First of all, these two surveys refer to slightly different periods, enrolling a different number of participants. Furthermore, we used non standardized questionnaires that were filled out by pediatricians from different parts of Italy, carrying out heterogeneous activities among all of them. Anyway, to the best of our knowledge, standardized and validated questionnaires on these topics are not currently available.