What are the considerations for treating pediatric asthma during the COVID-19 pandemic?

Abstract

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2, a coronavirus first identified at the end of 2019 in patients from Wuhan, China. More than 78 million COVID-19 cases and 1,7 million deaths have been unfortunately reported globally since the beginning of the pandemic to late December 2020. Based on currently available data, children appear to be affected less commonly than adults [1]. Although severe cases have been reported, symptoms appear to be milder in children than in adults. COVID-19 predominantly affects the lungs, and thus it is critically important to assess whether asthma, or other chronic lung diseases, place children at higher risk. The Centers for Disease Control and Prevention have reported moderate-to-severe asthma as an underlying medical condition at increased risk for severe COVID-19 in adults [2]. It is important to note that there are still conflicting data on asthma prevalence in COVID-19 patients. Although in preliminary studies from China and other countries asthma was underreported, in recent cohort studies the prevalence of asthma in adult patients with COVID-19 in the United States (US) ranged from 7.4% to 17% [3,4]; interestingly, asthma and the use of inhaled corticosteroids (ICS) were not associated with an increased risk of hospitalization in a US cohort of 1526 patients with COVID-19 [5]. Conversely, asthma and severe asthma were associated with COVID-19 mortality in an extensive analysis of United Kingdom patients’ electronic health records [6]. To date, few studies reported asthma as a potential risk factor for COVID-19 in children [7,8]. Underlying respiratory conditions, including asthma and chronic lung disease, have also been recently reported in pediatric patients with multisystem inflammatory syndrome in children (MIS-C), a newly recognized syndrome related to SARS-CoV-2 infection characterized by hyperinflammation and multiorgan involvement, presenting with clinical features similar to Kawasaki disease and toxic shock syndrome [9,10]. The pathophysiology of MISC is not well understood, and its link with certain underlying medical conditions (including asthma) remains to be further elucidated. Although very limited information is still available about the impact of asthma and whether it may increase the risk of severe illness from COVID-19 in children, some preliminary considerations may be drawn from the results of recent research conducted in children with asthma. Angiotensin-converting enzyme 2 (ACE-2) is the host cell receptor responsible for mediating infection by SARS-CoV-2; in addition to binding ACE2, priming of the viral spike (S) protein by the host serine protease TMPRSS2 is required for cell entry. Recent studies demonstrated that the expression of ACE2 in airway epithelium increases with age and seems to be modulated by the type of airway inflammation in patients with asthma. In particular, a lower ACE2 expression has been reported in children with or without asthma compared to adults and in patients with type 2 asthma rather than in nontype 2 asthma [11–13]. Furthermore, in vivo studies have shown a reduced gene expression of both ACE2 and TMPRSS2 in sputum among patients with asthma taking ICS, especially among those on higher doses [14]. These preliminary findings may represent potential mechanisms of reduced COVID-19 prevalence in children and patients with allergy and asthma. Eosinopenia is emerging as an early prognostic biomarker of severe COVID-19 in adults and children [15]. Our group demonstrated a significantly lower eosinophil count in children with COVID-19 than those with allergy and asthma [16]. Since eosinophilia plays a critical role in allergy and asthma pathogenesis, this evidence is consistent with the hypothesis that asthma or other allergic diseases do not seem to increase the risk for poor outcomes with SARS-CoV-2 infection in children. In this context, a recent study analyzing a cohort of children with allergic asthma in an area of high exposure to SARSCoV-2 found that asthmatic children with COVID-19 had a mild course of the infection independently from asthma severity [17]; however, the COVID-19 allergic asthmatic children required more rescue therapy with beta2-agonists and controller treatment than those without COVID-19, suggesting a possible role of SARS-CoV-2 in eliciting asthma exacerbation [17]. Still, there is no clear evidence of the role of SARS-CoV-2