Abstract
Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2. However, it is unclear if this reflects increased immune activation or increased immune residence in the nasal mucosa. We hypothesized that immune residency in the nasal mucosa of healthy individuals may differ across the age range. We applied single-cell RNA-sequencing and measured the cellular composition and transcriptional profile of the nasal mucosa in 35 SARS-CoV-2 negative children and adults, ranging in age from 4 months to 65 years. We analyzed in total of ~ 30,000 immune and epithelial cells and found that age and immune cell proportion in the nasal mucosa are inversely correlated, with little evidence for structural changes in the transcriptional state of a given cell type across the age range. Orthogonal validation by epigenome sequencing indicate that it is especially cells of the innate immune system that underlie the age-association. Additionally, we characterize the predominate immune cell type in the nasal mucosa: a resident T cell like population with potent antiviral properties. These results demonstrate fundamental changes in the immune cell makeup of the uninfected nasal mucosa over the lifespan. The resource we generate here is an asset for future studies focusing on respiratory infection and immunization strategies.
Highlights
Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2
While many hypotheses have been proposed to account for this discrepancy in age predilection of severe disease for SARS-CoV-25,6, a recent study demonstrated that the nasal mucosa, the site of viral exposure, of children and adults infected with SARS-CoV-2 is different in terms of the early immune response as measured by bulk RNA sequencing[7]
We characterized the composition of the nasal mucosa (NM) across the lifespan, by taking advantage of readily available clinical samples of NM-derived cells from 35 COVID-19-negative pediatric patients and healthcare workers
Summary
Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2 It is unclear if this reflects increased immune activation or increased immune residence in the nasal mucosa. This study found that children who have a similar viral burden to a cohort of adults had a transcriptional profile indicative of increased innate immune response with specific increases in Interferon, IL-1, IL-17, and NLRP3 s ignaling[7] This important insight offers information that may help explain the differences in disease severity between young and old populations, open questions remain. We take advantage of the increased coverage of the resident immune cell types in our younger samples and provided a deep characterization of a major immune cell type present in the nasal mucosa with potential antiviral properties
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