Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. Moreover, it has been demonstrated that ageing causes some modifications at a molecular level.
Objective The study aims to investigate a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people.
Methods We considered publicly available datasets on ageing-related genes and SARS-CoV-2 interactors. Then, for each SARS-CoV-2 protein interactor, we tested for the enrichment of ageing-related proteins. Finally, we performed a network-based analysis to identify which molecular mechanisms could play a role in the SARS-CoV-2 molecular aetiology and ultimately affect COVID-19 outcome.
Results We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes. Our analysis evidenced that virus infection particularly affects ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4.
Conclusion Our study generated a mechanistic framework aiming at explaining the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. This will provide testable hypotheses for future investigation on the mechanism of action of coronaviruses and pharmacological solutions tailored on specific age ranges.