Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range

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.

Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge

“…Furthermore, the milder condition in the younger patient cohort may be closely related to the potent innate immunity of the children. Previous studies (Vono et al, 2021;Winkley et al, 2021;Pierce et al, 2021), indicated that, compared with adults, younger children had a more robust mucosal response to prevent immune escape of the virus and generate an immediate barrier to viral infection. What is more, a recent study documented that the activated interferons in the respiratory mucosa of the children may protect them against SARS-CoV-2 infection (Yoshida et al, 2021), in which children had a significant increase of naive lymphocytes and decrease of NK cells in the systemic response, quite different from adults who had more cytotoxic T-cells (CTL) that were interferon-responsive cells.…”

Upregulated influenza A viral entry factors and enhanced interferon-alpha response in the nasal epithelium of pregnant rats

“…Though we investigated IAV receptors only in epithelial cells, we recognize that immune cells such as pDCs express them as well. However, we believe that the epithelial cells are the major source in the reproductive age group because the frequencies of epithelial cells outstrip the frequencies of immune cell populations in the nasal epithelium by a factor of approximately 10:1 [ 35 ]. Increased availability of these receptors could potentially promote enhanced entry of IAV into respiratory epithelial cells raising the possibility that pregnant women could be more susceptible to IAV infection, in addition to suffering from severe disease.…”

The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

“…Single cell sequencing analysis of upper airway cells reveal there are approximately twice as many cells that are ACE2 + /TMPRSS2than are ACE2 + /TMPRSS2 + (Supplementary Table S1) [32][33][34][35][36][37] . We considered whether the early replication advantage of Omicron in the hNEC was conferred by an expansion of the number of target cells available for initiation of infection, as the endosomal pathway enables ACE2 + /TMPRSS2cells to be infected.…”