The increased severity and mortality of SARS-CoV-2 infections in older individuals may be related to inflammageing – an age-associated phenomenon of increased general inflammation. In this Perspective, Arne Akbar and Derek Gilroy discuss this possibility as well as strategies to mitigate related effects. Inflammageing is thought to be caused, at least partially, by deterioration of aged cells (senescence) in tissues of the body that release inflammatory molecules. A growing number of studies show that excessive inflammation due to inflammageing combined with an aged immune system can inhibit overall immunity, which can also reduce vaccination efficacy in older people. According to Akbar and Gilroy, reducing the numbers of senescent cells with senolytic drugs or reducing inflammageing with anti-inflammatory drugs may be a beneficial strategy for improving COVID-19 outcomes in older patients. They also raise the question of whether vaccines can even be effective within these inflammatory environments. “The search for an effective vaccine for COVID-19 has also to consider the decreased vaccination efficacy in older subjects that may be associated with inflammageing. Therefore, the effective treatment of COVID-19 in older patients may require a combination of anti-inflammatory, anti-viral regimes to compliment vaccination against the virus,” write Akbar and Gilroy.