COVID-19 poses a substantially greater risk to older people with estimated 8-20% fatality rates in those >70 years (compared to ≈0.8% for influenza A). This suggests the immunological response to COVID-19 in older individuals leaves them dangerously susceptible to severe disease outcomes. We hypothesise this may be due to innate immune training, where aged individuals exhibit chronic inflammation and immune dysfunction mediated by epigenetic and functional reprogramming of cells in response to previous pathogen exposure. A greater understanding of these mechanisms is required given the burden of severe COVID-19 is mainly in the elderly.

Current immune-based therapeutics being trialed to treat severe COVID-19 disease (eg. IL-6 blockers) are aimed at inhibiting immune responses, however the use of these agents in individuals with impaired immune responses such as the elderly may be detrimental.

Currently there are no treatments identified that substantially prevent progression to severe disease. A better understanding of the mechanisms that dictate progression to severe disease, and why these processes may be heightened in the elderly, will identify specific immunological processes appropriate for therapeutic targeting and identify ways to predict and prevent severe disease.

Timeline

• 2020 -