How the Ageing Immune System May Kill COVID-19 Patients

The chronic inflammation experienced by healthy older people is likely to contribute to the increased COVID-19 mortality amongst the elderly, and may cause some T cells to attack the respiratory tract.

Inflammation is the body’s first line of defence against a pathogen. Inflammatory cells help keep an infection at bay while recruiting the more specialised cells of the adaptive immune system, such as T cells and B cells. However, excessive inflammation can not only damage surrounding tissue, but also appears to reduce the effectiveness of the adaptive immune response and, consequently, the effectiveness of vaccination.

This article published in the journal Science sets out how the increasing background inflammation that occurs with age, termed inflammageing, could contribute to the increased COVID-19 mortality seen amongst the elderly.

One hallmark of ageing is the accumulation of senescent cells in different tissues. Senescence occurs when a cell loses its ability to divide, and it enters a semi-dormant state in which it can release inflammatory molecules that are thought to contribute to inflammageing. The accumulation of these cells in the respiratory tract, as well as other inflammatory cells, could produce a baseline level of inflammation in older people that amplifies subsequent inflammation in severe COVID-19 cases.

Furthermore, it is possible that high levels of inflammation may actually turn T cells against the cells of the respiratory tract. This is because inflammatory molecules can make some cells (including senescent cells) produce ‘kill me’ signals called NKR ligands. This causes certain T cells to attack them, contributing to the respiratory damage seen in severe Covid, while also reducing their effectiveness against the virus.

More data is urgently needed to confirm to what extent these processes contribute to COVID-19 mortality. It is possible that drugs aimed at clearing senescent cells, called senolytics, might aid in the treatment or prevention of severe COVID-19. Findings would also have important implications for vaccine development: effective immunisation in older individuals may require anti-inflammatory and antiviral treatments to supplement vaccination.