Authors' response.

We thank Ciprandi et al for their salient points related to our recent article and description of their experiences with Italian patients. As they pointed out, children and those with allergy and asthma seem to be at a lower risk of coronavirus disease 2019 (COVID-19) and have milder disease. , Recently, however, a severe complication called multisystem inflammatory syndrome in children, which appears to be associated with COVID-19, has been described in pediatric patients. The incidence of this Kawasaki disease–like condition, its causes, and optimal management are still under investigation. Nonetheless, there is mounting evidence supporting a lower risk of COVID-19 among children in general.

Furthermore, there is now suggestive evidence that children and adults with allergic sensitization and asthma are protected from severe COVID-19 disease. It has been hypothesized that this may be related to the reduced nasal epithelial expression of angiotensin-converting enzyme 2, the receptor that severe acute respiratory syndrome coronavirus 2 uses for entry into host cells. In fact, a recent study using RNA sequencing found that angiotensin-converting enzyme 2 levels are lower in children with allergic sensitization and allergic asthma. However, it is important to note that although most studies in adults with COVID-19 have reported that asthma is uncommon, the Centers for Disease Control and Prevention reported that in children hospitalized and/or admitted to the intensive care unit for COVID-19, chronic lung disease (including asthma) was the most frequently documented comorbidity, which accounted for 40% of comorbidities. These studies have also not included details regarding asthma phenotypes, making it difficult to clarify the role that allergic disease plays in COVID-19 incidence and severity.

Ciprandi et al also discussed the role that eosinophils play in COVID-19, given the increasing use of biologics, which may cause eosinopenia for asthma treatment. Eosinopenia is not uncommon in patients with severe or fatal COVID-19. , Eosinopenia, however, seems to be a consequence of severe COVID-19 rather than a cause of severe disease. Acute inflammation suppresses eosinophil production and decreases eosinophil survival and activation. Type 1 interferons also lead to eosinophil apoptosis, and potent TH1 responses antagonize TH2 cytokines such as interleukin-5, a key mediator in eosinophil activation. Thus, we agree with the authors that asthma treatment, including biologics, should be continued in individuals who develop COVID-19, given that poor asthma control could increase the risk of adverse outcomes.

We agree that many questions remain unanswered, including whether an allergic disease is truly protective and how this protective effect is bolstered or dampened by asthma treatment, including biologics.