Asthma has a striking temporal character, in which time-of-day, patient age, and season each influence disease activity. The extent to which rhythms in asthma activity reflect exposure to specific disease triggers remains unclear. In this study, we examined how virus mitigation strategies enacted during the COVID-19 pandemic (“lockdown measures”) affected rhythms in asthma clinical activity in children. To this end, we retrospectively analyzed asthma clinical presentations in children aged <18 years to our regional academic medical center, comparing 4 years of medical records prior to COVID-19 lockdown measures with the 12 months immediately after the institution of such measures. We correlated these data to positive viral test results, febrile seizures, and allergic clinical surrogates (allergic reaction visits and Emergency Department [ED] antihistamine prescriptions, respectively) over the same time frame. In the 12 months following the institution of the COVID-19 lockdown, positivity rates for common respiratory viruses dropped by 70.2% and ED visits for asthma among children dropped by 62% compared to pre-COVID years. Lockdown suppressed seasonal variation in positive viral tests and asthma ED visits, while diurnal rhythms in asthma visits were unchanged. Asthma seasonality correlated most strongly with rhinovirus positivity both before and after the institution of COVID lockdown measures. Altogether, our data support a causal role for viruses in driving seasonal variability in asthma exacerbations in children.

Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive: robust in juvenile mice (4–6 wk old) but attenuated in mature mice (&gt;3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.

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