The ageing immune system and COVID-19

Deborah Dunn-Walters, Arne Akbar, Danny Altmann, Maria Elena Bottazzi, Judith Breuer, Siamon Gordan, Adrian Hayday, Tracy Hussell, Paul Klenerman, Clare Lloyd, Janet Lord, Paul Morgan, Peter Openshaw, Ruth Payne, Ultan Power, Eleanor Riley, Ken Smith, Ryan Thwaites, Xiao-Ning Xu, Doug BrownJennie Evans, Matthew Gibbard

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Since the beginning of the COVID-19 pandemic, it has been apparent that this disease affects different people in different ways. One of the starkest contrasts has been how infection with SARS-CoV-2 can affect people dissimilarly across age groups.

This report explores how ageing can affect the immune system’s response to the SARS-CoV-2 virus. This includes the role of ageing in susceptibility to infection, immune memory, what role other medical conditions associated with ageing have to play; what this means for the optimal treatment of COVID-19 and the vaccines that are being developed to prevent this disease. An asterisk (*) denotes words that appear in the glossary (annex 2).

It is well established that the immune system changes as we get older. The balance between immune activation, regulation and resolution can be altered as we age, resulting in inadequate protection against infection, along with a greater risk of inflammatory disease. As with many aspects of the human body, there is no one ‘cut off’ point for this to occur but instead it is a gradual process. Indeed, the shrinkage of the thymus, an organ that produces a type of immune cell known as T cells*, begins shortly after birth.

Large studies in the UK have confirmed the positive correlation between increasing age and increasing COVID-19 disease severity. Relative to hospitalised patients under 50 years of age, those aged 60–69 are approximately five times more likely to die from COVID-19, while those aged 70–79 are at 8.5 times greater risk. The reasons for this are numerous. There are, for example, increased and chronic background levels of inflammation in older individuals, referred to as ‘inflammaging’*, which have been linked to increased risk of disease and increased expression of inflammatory genes is associated with increased all-cause mortality in older individuals.

Various factors work in tandem with the ageing immune system to exacerbate effects that are already happening. One feature influencing the age-related severity of COVID-19 is the higher prevalence of chronic disease in this population: by the age of 70 years, 75% of adults have two or more long-term conditions, termed multimorbidity. This can include chronic lung disease, diabetes and hypertension, amongst other conditions, all of which contribute to a greater risk of poor outcomes from COVID-19. More data is needed to be able to confirm if co-infection with either other viruses or bacteria results in an increase in mortality or morbidity.

Immunity to SARS-CoV-2 is not fully understood at any age and more work needs to be done here to determine the correlates of protection and then carry out follow-up studies to determine the lifespan of immunity. Looking at immunity in older people we can, however, look to prior knowledge on other infections and vaccine studies, which could suggest that raising robust immunity may be more difficult or may take longer.

A key aspect of an ageing immune system is a change in its response to vaccines. The decline in immune function in older adults can lead to both a reduced initial response to vaccination and/or reduced efficacy of the vaccine response. Continuing to work on the development of therapeutics for those who have contracted COVID-19 is vitally important because of concerns over the ability of older people to develop effective immunity or to respond to a vaccine.

It is as yet unknown whether older people will require different vaccines or an altered dosing schedules, but this will have real consequences for the public health response to this pandemic. Such knowledge will affect the deployment of vaccines once one or more is proven to be safe and effective. It is therefore of the utmost urgency that those making policy decisions have an understanding of age differences in immunity and a clear plan for action, including public information and education.
Original languageEnglish
PublisherBritish Society for Immunology
Number of pages17
Publication statusPublished - 10 Nov 2020


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