SARS-CoV-2 in Asthmatic Children: Same Consequences in Different Endotypes?

Abstract

During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, concerns arose regarding the susceptibility of asthmatic children, one of the most common chronic conditions in childhood and a major cause of hospitalization in pediatric settings. Unexpectedly, evidences showed milder clinical courses and fewer asthma exacerbations in these patients, even if cases of critical and fatal infection, often related to specific clinical features of the patient, are not negligible. In this regard, obesity is considered not only an important comorbidity in patients with difficult-to-treat asthma but also a risk factor for more severe forms of COVID-19. These observations are of even greater concern in the context of an increase in childhood obesity that began even before the SARS-CoV-2 pandemic and has continued also as a consequence of it. Given asthma's heterogeneity, especially in children, an endotype-based approach is crucial. This is possible through a detailed analysis of the complex metabolic pathways that correlate asthma, COVID-19 infection and obesity thanks to new high-through-put technologies, especially metabolomics, which with minimally invasive sampling, including on exhaled breath condensate (EBC), can provide precise and unbiased evidence in support of existing endotypes, making it possible to identify not only the most vulnerable individuals and thus risk stratification through specific biomarkers, but also new molecular and therapeutic targets. This review explores asthma endotypes by highlighting their shared immunometabolic pathways with COVID-19. Findings suggest that metabolomics could enable more accurate risk stratification and guide personalized interventions during viral pandemics, especially in the presence of relevant comorbidities such as obesity.

Keywords: SARS-CoV-2; asthma endotypes; metabolomics; obesity; pediatric asthma; precision medicine; risk stratification.

Figure 1

Clinical, metabolomic and immunologic features of pediatric asthma endotypes in relation to COVID-19 susceptibility. Abbreviations: EBC—exhaled breath condensate; ↓—decreased; ↑—increased; Th2—T helper type 2; ICS—inhaled corticosteroids; ACE2—angiotensin-converting enzyme 2; TMPRSS2—transmembrane protease, serine 2; Th17—T helper type 17 cells; IFN—interferon; IL-6—interleukin 6; IL-33—interleukin 33; ILC2—Type 2 innate lymphoid cells; PUFA—polyunsaturated fatty acids.