Studies Show SARS-CoV-2 Shows Different Affinity for Nasal Epithelial Cells with Age

In a recent study posted on Bio Rxiv*In a preprint server, researchers investigated the relationship between the development of goblet inflammatory cells and the age-related pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background

The nasal epithelium is a major barrier to inhalation infection, and nasal epithelial cells (NECs) serve as a major target for coronavirus disease 2019 (COVID-19) infection. Infection of upper airway cells can spread distally, resulting in extensive alveolar damage and long-term consequences, including the incidence of pulmonary fibrosis.

Current research shows that a pre-activated antiviral interferon (IFN) state within the upper respiratory epithelium protects children from infection to some extent. This may partly explain why children are better protected, but it does not fully explain the age-related increase in infection risk among adults. Investigation of epithelial infection and subsequent repair against 19 could yield innovative therapeutics against COVID-19 and future respiratory virus risks.

About research

In the present study, investigators evaluated changes in cellular topography and function in nasal epithelial cells of children, adults, and the elderly infected with SARS-CoV-2.

Fresh nasal brushes were obtained from humans for this study. Her four matched nasal brush specimens from children were recruited for single-cell ribonucleic acid sequencing (scRNA-sequencing) analysis. The team used his SARS-CoV-2 isolate (hCoV-19/England/2/2020) for infection. The African green monkey kidney cell line Vero E6 was used for virus propagation.

Additionally, the team quantified viral load By plaque assay, virus copy number was quantified by quantitative real-time polymerase chain reaction (PCR). We then combined live-cell microscopy, proteomics, immunofluorescence labeling, and gene expression analysis to estimate the phenotypic impact of epithelial cell infection across age groups.

result

In healthy, uninfected control cultures, the proportions of several epithelial cell types changed with age. The proportions of the basal/progenitor (KRT5hi) subtype in the adult and geriatric culture datasets were 36.5% and 35.3%, respectively, but 13.8% in the pediatric culture dataset. Aged and adult cultures had the highest number of basal 1 and 2 cells and were virtually absent in pediatric cultures. All age groups showed comparable apical differentiation, such as mucus (MUC5AC) production, along with similar amounts of cilia, no marked variation in ciliary beating frequency (CBF), and changes in cell motility with increasing age. There was no

The most obvious change in pediatric cultures was an increase in the number of goblet cells, particularly the goblet 2 subset. This indicated a change in cellular status from secretory cells found in aged and adult cultures to goblet cells containing higher levels of bactericidal/increased permeability fold-containing group A member 1 (BPIFA1) .

Importantly, the research team found no differences in protein levels associated with viral entry factors in age-related samples, but the highest transmembrane protease serine 2 (TMPRSS2) expression required for SARS-CoV-2 spike (S) protein priming 26 and highest levels of angiotensin-converting enzyme-2 (ACE-2) consisting of the viral S protein binding site required for viral entry .

Secretory and basal type 2 cells also showed the highest TMPRSS2 and ACE2 expression in adult and elderly patient cultures. This indicated an age-related change in susceptibility to viral infection from goblet cells to secretory cells. Basidin (BSG), Neuropilin-1 (NRP1), NRP2, Cathepsins L (CTSL), and FURIN showed similar patterns to ACE2 and TMPRSS2.

The most prominent cellular change after infection was the emergence of Goblet 2 inflammatory cells, absent in mock-infected pediatric samples but not in aged or adult cultures. In addition, the Goblet 2 inflammatory cell type had higher abundance of IFN-inducible proteins, including tetratricopeptide repeat 1 (IFIT1), IFIT3, and CXCL10, than other Goblet cell subtypes, indicating a significant interaction with type I IFN signaling. shows relevance.

Also, epithelial cell samples from infected elderly individuals showed elevation near basal cells infected with SARS-CoV-2 compared to mock cultures, suggesting that elderly-specific progenitors in response to SARS-CoV-2 infection Shows cell recruitment (proliferation).

The team also noted that SARS-CoV-2-infected elderly NECs exhibited significantly faster wound healing rates than infected pediatric cultures, suggesting that cell motility, another manifestation of defective repair mechanisms, may be impaired. suggests an increase. Wound healing rates in elderly samples infected with SARS-CoV-2 were significantly faster than in comparable sham-infected cultures. Pediatric NECs infected with SARS-CoV-2 showed significantly delayed wound healing rates than corresponding mock-infected cultures.

Conclusion

The results of this study showed that SARS-CoV-2 tropism for nasal epithelial cells changed with age, favoring infection of pediatric goblet or adult secretory cells. Infected pediatric goblet cells showed a significant innate SARS-CoV-2 antiviral response triggered by interferon and less infectious virions compared to aged cultures. These findings provided new insights into the pathophysiology of COVID-19 during aging and showed how defective repair increases SARS-CoV-2 infection in the elderly.

*Important Notices

bioRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .