The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma are not well understood. We investigated whether the ambient levels of fine PM with aerodynamic diameter ≤ 2.5 microns (PM 2.5) are associated with alterations in circulating monocytes in children with or without asthma. Increased exposure to ambient PM 2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or LPS. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

Background: The global epidemiology of asthma among COVID-19 patients presents striking geographic differences defining high and low [asthma and COVID-19] co-occurrence prevalence zones (1). The objective of the present study was to compare asthma prevalence among hospitalized COVID-19 patients in major global hubs across the world with the application of common inclusion criteria and definitions. Methods: We built a network of six academic hospitals in Stanford (Stanford University)/USA, Frankfurt (Goethe University), Giessen (Justus Liebig University) and Marburg (Philipps University)/Germany, and Moscow (Clinical Hospital 52 in collaboration with Sechenov University)/Russia. We collected clinical and laboratory data for patients hospitalized due to COVID-19. Comorbidities reported were based on the 2020 International Classification of Diseases-10th Revision codes. Results: Asthmatics were overrepresented among hospitalized COVID-19 patients in Stanford and underrepresented in Moscow and Germany as compared to the prevalence among adults in the local community. Asthma prevalence was similar among ICU and hospital non-ICU patients, which implied that the risk for developing severe COVID-19 was not higher among asthmatics. The number of males and comorbidities was higher among COVID-19 patients in the Stanford cohort, and the most frequent comorbidities among these asthma patients were other chronic inflammatory airway disorders such as chronic obstructive pulmonary disease (COPD). Conclusion: Observed disparity in COVID-19-associated risk among asthmatics across countries and continents is connected to varying prevalence of underlying comorbidities, particularly COPD. Public health policies in the future will need to consider comorbidities with an emphasis on COPD for prioritization of vaccination and preemptive treatment.

Background: It is unclear if asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. Methods: All patients testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. Results: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4·15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1·12 [95% CI 0·86, 1·45], p=0·40). Among SARS-CoV-2 positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared to non-allergic asthma (OR 0·52 (0·28, 0·91), p=0·026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared to patients with mild or asymptomatic disease, independent of asthma status (p=0.0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. Conclusions: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared to non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms three months post-infection.