Differences in how young and elderly people’s nasal cells respond to the SARS-CoV-2 virus may explain why children typically experience milder COVID-19 symptoms.
The finding comes from a study funded by UK Research and Innovation, the National Institute for Health and Care Research, Great Ormond Street Hospital Biomedical Research Centre, Wellcome and the Chan Zuckerberg Foundation.
The study focused on the early effects of SARS-CoV-2 infection on the cells first targeted by the viruses, called human nasal epithelial cells (NECs). The cells were donated by healthy participants from Great Ormond Street Hospital, University College London Hospital and the Royal Free Hospital. The participants included children under the age of 11, adults aged 30 to 50 and, for the first time, adults over the age of 70.
Using single-cell RNA sequencing techniques that enable scientists to identify the unique genetic networks and functions of thousands of individual cells, the team identified 24 distinct epithelial cell types. Cultures from each age group were then either mock infected or infected with SARS-CoV-2.
The research, published in Nature Microbiology, found that after three days the NECs of children responded quickly to SARS-CoV-2 by increasing interferon, the body’s first line of anti-viral defence, restricting viral replication. However, this early anti-viral effect became less pronounced with age.
The researchers also found that NECs from elderly individuals not only produced more infectious virus particles, but also experienced increased cell shedding and damage. The strong antiviral response in the NECs of children could explain why younger people typically experience milder symptoms. In contrast, the increased damage and higher viral replication found in NECs from elderly individuals could be linked to the greater severity of the disease observed in older adults.
Project lead, Dr Claire Smith, from the UCL Great Ormond Street Institute of Child Health, said: “Our research reveals how the type of cells we have in our nose changes with age, and how this affects our ability to combat SARS-CoV-2 infection. This could be crucial in developing effective anti-viral treatments tailored to different age groups, especially for the elderly who are at higher risk of severe COVID-19.”
- Woodall MNJ, Cujba AM, Worlock KB et al. Age-specific nasal epithelial responses to SARS-CoV-2 infection. Nat Microbiol Published online April 15, 2024 doi:10.1038/s41564-024-01658-1.