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New BSI COVID-19 immunology report: The ageing immune system and COVID-19

The BSI’s Immunology and COVID-19 taskforce has been hard at work since the release of its last briefing note in August to produce a report on the ageing immune system and COVID-19. The rapid review style document lays out how what we do and don’t currently know about how ageing can affect the immune system’s response to COVID-19. In this article, our Policy & Public Affairs Manager, Matthew Gibbard, discusses the findings of this report and explains its importance, both for the BSI’s policy work and mission, and for optimising patient care, treatment and vaccine approaches. You can read the news story accompanying the report launch on our website.

Engaging with policymakers

The importance of these reports is twofold. Firstly, it allows us to communicate with policymakers in a way that few other organisations are able to. By taking topics that are hugely relevant to public discourse at the moment, we hope to improve the level of debate in the public arena, inform decisionmaking by those in power, and improve the quality of scrutiny of governments by the national legislatures, through presenting the latest science and research in an accessible and informative way.

Secondly, by engaging with policymakers on these hugely important topics, we have established ourselves as a thought leader in the COVID-19 and immunology policy space. Through this, we have become an organisation that is actively sought out by senior parliamentarians to provide briefings on other topics, such as COVID-19 vaccine development, and we are working hard to ensure that this name recognition continues beyond the pandemic so that we can better represent the immunology community in the years to come.

Focus on ageing

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. The fascinating science behind this combined with the policy implications including but not limited to, transmission and susceptibility, therapeutics and vaccines, durability and longevity of immunity, made this an obvious choice of topic for the taskforce to tackle. The 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. The report outlines five research recommendations to help increase our knowledge of the role played by the ageing immune system in the body’s response to COVID-19. A better understanding of the immunological response in older people to COVID-19 infection will help us improve patient care and has implications for treatment and vaccine approaches.

COVID-19 severity and ageing

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 which is associated with increased allcause mortality in older individuals.

Factoring in multimorbidity

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, among 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.

Response to vaccines

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 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.

Research priorities

  1. Studies on the symptoms and clinical progression of COVID-19 infection should include non-hospitalised individuals and be large enough to determine ages at which critical changes occur. Studies should identify correlates that affect initial infection, progression to severe disease, recovery and re-infection. This information is essential to determine which age groups need which interventions, enabling targeting of interventions to specific groups. For example, at what age – and with which additional risk factors – is shielding required? What role do antivirals and anti-inflammatory drugs have at different ages?

  2. Identification of the extent of the immune system contribution to the symptoms and pathology of the disease is required in order to identify areas for possible intervention without compromising anti-infection activity.

  3. We urgently need to establish reliable and tractable methods to measure immune responses in patients following infection or vaccination with a specific focus on different age groups. We must include measures of cellular immunity as well as humoral immunity*. More studies are needed in the community setting to capture different degrees of disease severity, to identify what ‘good’ looks like in an asymptomatic immune response. Studies should extend into the convalescent period and beyond to establish factors that affect the duration of effective immunity.

  4. Studies are needed to determine the effect of other challenges to the immune system during COVID-19 infection. This includes studies of co-infection, in particular because older people often live with, for example, bacterial urinary tract infections or CMV* infections. Similarly, the consequences of acute co-infections with other respiratory viruses, such as influenza virus and RSV, on COVID-19 disease severity needs to be examined. Finally, the effect of vaccination against other pathogens, such as influenza, pneumococcal disease or TB, on the response to SARS-CoV-2 requires clarification.

  5. Vaccine protocols need to be optimised for older adults by investigating dose, formulation, boosting and vaccination routes. Different groups of people, by age or by comorbidity, may require different types of vaccine or vaccine formulations.

Download the full report from our website here.

The project has also been condensed into a question and answer blog, which is more accessible for those without a research background. You can read a summary of the main points here.

Our huge thanks to all members of our Immunology and COVID-19 taskforce who gave their time to contribute to this work. Our expert advisory group aims to identify the immunology research priorities to guide future studies and treatments and inform public health measures to control the Coronavirus spread. Find out more here.

Matthew Gibbard
BSI Policy & Public Affairs Manager